Pharmacology (Full Deck) Flashcards
What is the frequency of emesis for an agent with a minimal emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- <10%
What is the frequency of emesis for an agent with a low emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- 10-30%
What is the frequency of emesis for an agent with a moderate emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- 30-90%
What is the frequency of emesis for an agent with a high emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- >90%
What drugs are in the anthracycline class?
Drugs in this class are:
- Daunorubicin
- Daunorubicin Liposomal
- Daunorubicin and Cytarabine Liposomal
- Doxorubicin
- Doxorubicin Liposomal
- Idarubicin
- Epirubicin
- Valrubicin
What is the brand name of Daunorubicin?
The brand name of this generic drug is:
- Daunomycin
What is the brand name of Daunorubicin Liposomal?
The brand name of this generic drug is:
- DaunoXome
What is the brand name of Daunorubicin and Cytarabine Liposomal?
The brand name of this generic drug is:
- Vyxeos
What is the brand name of Doxorubicin?
The brand name of this generic drug is:
- Adriamycin
What is the brand name of Doxorubicin Liposomal?
The brand name of this generic drug is:
- Doxil
What is the brand name of Idarubicin?
The brand name of this generic drug is:
- Idamycin
What is the brand name of Epirubicin?
The brand name of this generic drug is:
- Ellence
What is the brand name of Valrubicin?
The brand name of this generic drug is:
- Valstar
What is the generic of name of Daunomycin?
The generic name of this brand name drug is:
- Daunorubicin
What is the generic of name of DaunoXome?
The generic name of this brand name drug is:
- Daunorubicin Liposomal
What is the generic of name of Vyxeos?
The generic name of this brand name drug is:
- Daunorubicin and Cytarabine Liposomal
What is the generic of name of Adriamycin?
The generic name of this brand name drug is:
- Doxorubicin
What is the generic of name of Doxil?
The generic name of this brand name drug is:
- Doxorubicin Liposomal
What is the generic of name of Idamycin?
The generic name of this brand name drug is:
- Idarubicin
What is the generic of name of Ellence?
The generic name of this brand name drug is:
- Epirubicin
What is the generic of name of Valstar?
The generic name of this brand name drug is:
- Valrubicin
What is the class and MOA of Daunorubicin?
This drug in the following class:
- Anthracycline
This drug’s MOA is as follows:
- Inhibits DNA and RNA synthesis via:
- Intercalation (direct binding to DNA)
- Inhibition of topoisomerase II (a repair enzyme)
- Steric obstruction
What is the class and MOA of Doxorubicin?
This drug in the following class:
- Anthracycline
This drug’s MOA is as follows:
- Inhibits DNA and RNA synthesis via:
- Intercalation (direct binding to DNA)
- Inhibition of topoisomerase II (a repair enzyme)
- Steric obstruction
What is the class and MOA of Idarubicin?
This drug in the following class:
- Anthracycline
This drug’s MOA is as follows:
- Inhibits DNA and RNA synthesis via:
- Intercalation (direct binding to DNA)
- Inhibition of topoisomerase II (a repair enzyme)
- Steric obstruction
What is the class and MOA of Epirubicin?
This drug in the following class:
- Anthracycline
This drug’s MOA is as follows:
- Inhibits DNA and RNA synthesis via:
- Intercalation (direct binding to DNA)
- Inhibition of topoisomerase II (a repair enzyme)
- Steric obstruction
What is the class and MOA of Valrubicin?
This drug in the following class:
- Anthracycline
This drug’s MOA is as follows:
- Inhibits DNA and RNA synthesis via:
- Intercalation (direct binding to DNA)
- Inhibition of topoisomerase II (a repair enzyme)
- Steric obstruction
What is the emetic potential of Daunorubicin?
The emetic potential of this drug is:
- Moderate
What is the emetic potential of Daunorubicin Liposomal?
The emetic potential of this drug is:
- Low
What is the emetic potential of Daunorubicin and Cytarabine Liposomal?
The emetic potential of this drug is:
- Moderate
What is the emetic potential of Doxorubicin?
The emetic potential of this drug is:
- Moderate if <60 mg/m2
- High if >60 mg/m2
What is the emetic potential of Doxorubicin Liposomal?
The emetic potential of this drug is:
- Low
What is the emetic potential of Idarubicin?
The emetic potential of this drug is:
- Moderate
What is the emetic potential of Epirubicin?
The emetic potential of this drug is:
- Moderate (pediatrics and adults)
- High when used in combination with cyclophosphamide (adults)
What is the emetic potential of Valrubicin?
The emetic potential of this drug is:
- Minimal
Describe the emetic potential of the Anthracycline class.
The emetic potential of this drug class is:
- Mainly moderate (Daunorubicin, Doxorubicin (<60 mg/m2), Doxorubicin and Cytarabine, Idarubicin, Epirubicin)
- High for Doxorucibin >60 mg/m2, and Epirubcin when used in combination with Cyclophosphamide (adults)
- All the others are low (Daunorubicin Liposomal, Doxorubicin Liposomal) or minimal (Valrubicin)
What drugs in the Anthracycline class have a high emetic potential?
Drugs in the class with a high emetic potential are:
- Doxorucibin >60 mg/m2
- Epirubcin when used in combination with Cyclophosphamide (adults)
What drugs in the Anthracycline class have a moderate emetic potential?
Drugs in the class with a moderate emetic potential are:
- Daunorubicin
- Doxorubicin (<60 mg/m2)
- Doxorubicin and Cytarabine
- Idarubicin
- Epirubicin
What drugs in the Anthracycline class have a low emetic potential?
Drugs in the class with a low emetic potential are:
- Daunorubicin Liposomal
- Doxorubicin Liposomal
What drugs in the Anthracycline class have a minimal emetic potential?
Drugs in the class with a minimal emetic potential are:
- Valrubicin
What are the main indications of Daunorubicin?
The main indications of this drug are:
- ALL
- AML
- Kaposi sarcoma (Daunorubicin Liposomal)
What are the main indications of Daunorubicin Liposomal?
The main indications of this drug are:
- Kaposi sarcoma
What are the main indications of Daunorubicin and Cytarabine Liposomal?
The main indications of this drug are:
- AML
What are the main indications of Doxorubicin?
The main indications of this drug are:
- AML
- Bladder Cancer
- Breast Cancer
- Hodkin Lymphoma
- Non-Hodkin Lymphoma
- Osteosarcoma
- Soft Tissue Sarcomas
What are the main indications of Doxorubicin Liposomal?
The main indications of this drug are:
- Breast Cancer
- Kasposi Sarcoma
- Ovarian Cancer
What are the main indications of Idarubicin?
The main indications of this drug are:
- AML
What are the main indications of Epirubicin?
The main indications of this drug are:
- Breast Cancer
- Bladder Cancer
- Soft Tissue Sarcomas
What are the main indications of Valrubicin?
The main indications of this drug are:
- Bladder Cancer
What are the main/common indications of the Anthracycline class?
The main/common indications of this drug class are:
- Doxorubicin is the workhourse
- AML
- Bladder Cancer
- Breast Cancer
- Hodkin Lymphoma
- Osteosarcoma
- Soft Tissue Sarcomas
What are the notable/common monitoring parameters for the Anthracycline class?
The notable/common monitoring parameters for this drug class are:
- Echocardiogram to assess left ventricular ejection fraction (LVEF) prior to start of therapy, repeat if S/Sx of HF
- History and cardiac exam prior to every cycle
What drug(s) require cardiac surveillance and monitoring for heart failure?
Drug(s) requiring this monitoring are:
- Anthracyclines
Describe the extravasation risk and management strategies for the Anthracycline class.
The extravasation risk and mangement strategies for this drug class are as follows:
- All Anthracyclines are vesicants except for Valrubicin (intra-vesical) and liposomal products.
- For intravenous administration only through a free flowing central IV line: not for intramuscular or subcutaneous administration.
- If extravasation occurs, stop infusion, aspirate, give antidote (dexrazoxane [Totect] 1000 mg/m2 via remote IV site over 1-2 hours x 2 days or dimethyl sulfate [DMSO]), apply dry cold compresses.
What are the notable/common ADRs of the Anthracycline class?
The notable/common ADRs of this drug class are:
- Cardiac toxicity (through reactive oxygen species, apoptosis, DNA damage (via topoisomerase II inhibition), and inhibition of protein synthesis
- Body fluid discoloration (urine, tears, sweat, and saliva)
What are the risk factors for developing cardiac toxicity with an Anthracycline?
Risk factors for developing this ADR with this drug class are:
- High cumulative exposure (most consistent risk factor)
- Older age (>65 years)
- Very young age (<4 years)
- Female gender
- Pre-existing cardiovascular disorders and comorbidities:
- Hypertension
- Smoking
- Hyperlipidemia
- Obesity
- Diabetes
What is the recommended maximum lifetime dose of Anthracyclines?
The recommended maximum lifetime dose of this class is:
- 450-550 mg/m2 Doxorubicin equivalents
Describe the strategy and rationale for management of cardiac toxicity caused by Anthracyclines.
The strategy and rationale for management of this condition caused by this drug class are:
- Limit lifetime exposure (<450-550 mg/m2 Doxorubicin equivalents)
- Perform baseline testing (echocardiogram)
- Dexrazoxane (Zinecard) can be used for prevention.
Describe the use of dexrazoxane in the management of cardiac toxicity associated with Anthracyclines.
The use of this drug in the management of cardiac toxicity associated with this class is as follows:
- Given IV in a 10:1 ratio of dexrazoxane:doxorubicin.
- Doxorubicin must be administered within 30 minutes of the completion of the dexrazoxane infusion.
- Its FDA labeled indication is in women with metastatic breast cancer with a cumulative doxorubicin dose exceeding 300 mg/m2.
- May also be used off label and in some pediatric protocols.
- It is not recommended for use with initial doxorubicin therapy.
- Dexrazoxane is marketed under two different brand names (Totect and Zinecard), however they are not interchangeable.
- Totect is indicated for Anthracycline extravasations.
- Generic dexrazoxane and Zinecard are indicated for reducing doxorubicin-induced cardiomyopathy.
Describe the strategy and rationale for management of urine discoloration caused by Anthracyclines.
The strategy and rationale for management of this condition caused by this drug class are:
- This discoloration is harmless and will resolve 1-2 days after the anthracycline dose
- Patients should be counselled that urine discoloration from an anthracycline should be painless. If the discoloration (especially if red) is accompanied by symptoms such as urgency, frequency, or discomfort, they should be evaluated by their healthcare provider as these could be signs of blood in the urine.
Describe the metabolism of the Anthracycline class.
The metabolism of this drug is as follows:
- All drugs in this class are hepatically metabolized and generally require dose adjustments in patients with hepatic dysfunction
What agent was given the nickname “the red devil” and why?
This nickname was given to this drug due to its bright red color, vesicant properties, and side-effect profile.
What is the nickname given to Doxorubicin and why?
This drug was the nickname “the red devil” due to its bright red color, vesicant properties, and side-effect profile.
What drugs are in the anti-tumor antibody class?
Drugs in this class are:
- Bleomycin
What is the brand name of Bleomycin?
The brand name of this generic drug is:
- Blenoxane
What is the generic of name of Blenoxane?
The generic name of this brand name drug is:
- Bleomycin
What are the main indications for use of Bleomycin?
The main indications of this drug are:
- Hodgin Lymphoma
- Testicular Cancer
- Ovarian Germ Cell Cancer
What is the class and MOA of Bleomycin?
This drug in the following class:
- Anti-tumor antibody
This drug’s MOA is as follows:
- Inhibits synthesis of DNA by binding to DNA leading to single- and double-strand breaks.
What are the notable monitoring parameters for Bleomycin?
The notable monitoring parameters for this drug are:
- Pulmonary function tests before, during and after chemotherapy
What drug(s) notably require monitoring for pulmonary function tests?
Drug(s) requiring this monitoring are:
- Bleomycin
What is the emetic potential of Bleomycin?
The emetic potential of this drug is:
- Minimal
Describe the extravasation risk and management strategies for Bleomycin.
The extravasation risk and mangement strategies for this drug are as follows:
- None; N/A
Describe the administration of Bleomycin.
The administration of this drug is described as follows:
- Can be given IM, SubQ, and intrapleural
- Due to the possibility of an anaphylactoid reaction, the manufacturer recommends administering test dose of 2 units or less before the first 2 doses. If no acute reaction occurs, then the regular dosage schedule may be followed. Monitor carefully, particularly following the first 2 doses.
Describe the metabolism of Bleomycin.
The metabolism of this drug is as follows:
- Metabolized by enzymatic inactivation by bleomycin hydrolase which is widely distributed in normal tissues (except for the skin and lungs)
- Cleared/excreted in urine
What are the notable ADRs of Bleomycin?
The notable ADRs of this drug are:
- Pulmonary toxicity (Bleomycin hydrolase is not found in the lungs).
- Interstitial pneumonitis is the most common form of bleomycin pulmonary toxicity but it can also progress to pulmonary fibrosis
which is irreversible and potentially fatal.
- A severe idiosyncratic reaction consisting of HTN, mental confusion, fever, chills, and wheezing has been reported in approximately 1% of lymphoma patients treated with Bleomycin
What drug(s) is notable for causing pulmonary toxicity?
The drugs notable for cause this condition are:
- Bleomycin
Describe the strategy and rationale for management of pulmonary toxicity caused by Bleomycin.
The strategy and rationale for management of this condition caused by this drug are:
- Routinely follow pulmonary function tests, including DLCO (diffusing capacity of the lung for carbon monoxide) during therapy and discontinue if there are significant changes in pulmonary function, including a decrease
in DLCO of 40-60%.
What are the risk factors for developing pulmonary toxicity with Bleomycin?
Risk factors for developing this ADR with this drug/class are:
- Age >70 years
- Cumulative lifetime dose of >400 units
- Use of GCSF
What is the threshold lifetime dose of Bleomycin?
The threshold lifetime dose of this drug is:
- 400 units
- Beyond this, the risk of pulmonary toxicity increases
Describe the half-life of Bleomycin.
The half-life of the this drug is described as follows:
- ~2 hours but increases exponentially as CrCl decreases
What are the clinical pearls of Bleomycin?
The clinical pearls of this drug are as follows:
- Guidelines do not recommend the routine use of GCSF during bleomycin therapy when used for the treatment
of lymphoma especially since ABVD (Doxorubicin + Bleomycin + Vinblastine + Dacarbazine) can be safely given at full dose intensity without GCSF use.
- No increased risk of pulmonary toxicity with GCSF + Bleomycin for the treatment of testicular cancer, thus use of GCSF is acceptable (although still not recommended as primary prophylaxis).
- In patients on ABVD for Hodgkin lymphoma, bleomycin can be dropped if there is a positive response (Deauville 1 or 2) on interim PET scan after 2 cycles. In this situation, continuing with just AVD for the remaining cycles is safer (from a pulmonary toxicity standpoint) but no less effective.
- Due to the possibility of an anaphylactoid reaction, the manufacturer recommends administering a test dose before the first 2 doses
What drugs are in the Folate Antagonist class?
Drugs in this class are:
- Methotrexate
- Pemetrexed
What are the main cancer-related indications for use of Methotrexate?
The main cancer-related indications of this drug are:
- ALL
- Non-Hodgkin Lymphoma
- GVHD
- Bladder Cancer
- Head and Neck Cancer
- Osteosarcoma
- Soft Tissue Sarcoma
What are the main indications for use of Pemetrexed?
The main indications of this drug are:
- Bladder Cancer
- Mesothelioma
- NSCLC
What is the class and MOA of Methotrexate?
This drug in the following class:
- Folate antagonist
This drug’s MOA is as follows:
- Inhibits dihydrofolate reductase thus inhibiting the formation of reduced folates.
- Inhibits thymidylate synthetase thus inhibiting synthesis of purines and thymidylic acid.
- All this leads to inhibition of DNA synthesis, repair, and cellular replication
What is the class and MOA of Pemetrexed?
This drug in the following class:
- Folate antagonist
This drug’s MOA is as follows:
- Inhibits dihydrofolate reductase thus inhibiting the formation of reduced folates.
- Inhibits thymidylate synthetase thus inhibiting synthesis of purines and thymidylic acid.
- All this leads to inhibition of DNA synthesis, repair, and cellular replication
What are the notable monitoring parameters for Methotrexate?
The notable monitoring parameters for this drug are:
- Methotrexate levels with high dose (>500 mg/m2) - monitor daily until cleared
- Urine pH with high dose
What drug(s) notably require monitoring for urine pH?
Drug(s) notably requiring this monitoring are:
- Methotrexate
What drug(s) notably require monitoring for drug levels daily until cleared?
Drug(s) notably requiring this monitoring are:
- Methotrexate
Describe the administration of Methotrexate.
The administration of this drug is described as follows:
- Most methotrexate protocols will require the urine pH to be >7 before starting methotrexate.
- Alkalization protocols vary per institution but often include IV fluids, sodium bicarbonate (either IV or oral) and/or acetazolamide.
What is the emetic potential of Methotrexate?
The emetic potential of this drug is:
- Minimal with low lose (<50 mg/m2)
- Low with low-moderate doses (50-250 mg/m2)
- High with moderate-high doses (>250 mg/m2)
What is the emetic potential of Pemetrexed?
The emetic potential of this drug is:
- Low
Describe the extravasation risk and management strategies for Methotrexate.
The extravasation risk and management strategies for this drug are as follows:
- None; N/A
Describe the extravasation risk and management strategies for Pemetrexed.
The extravasation risk and management strategies for this drug are as follows:
- None; N/A
Describe the metabolism of Methotrexate.
The metabolism of this drug is as follows:
- Minimal metabolism; excreted primarily (90%) in the urine as unchanged drug
- Urine clearance is pH dependant and improved when the urine is alkalized
- High dose methotrexate may “third space” or accumulate in fluid collections leading to prolonged methotrexate clearance and increased toxicity. Patients with ascites. pericardial effusions. pleural effusions or other fluid collections should not receive high
dose methotrexate until those have been drained.
Describe the metabolism of Pemetrexed.
The metabolism of this drug is as follows:
- Minimal metabolism; excreted primarily (90%) in the urine as unchanged drug
What are the notable ADRs of Methotrexate?
The notable ADRs of this drug are:
- Methotrexate toxicity
- Renal dysfunction
- Bone marrow suppression
- Mucositis
What are the notable ADRs of Pemetrexed?
The notable ADRs of this drug are:
- Main one is that serious and occasionally fatal dermatologic toxicity may occur
- Others are myelosuppression, renal dysfunction, and GI toxicities (especially with concomitant Ibuprofen use)
Describe the strategy and rationale for management of Methotrexate toxicity.
The strategy and rationale for management of this condition caused by this drug are:
- Ensure urine is adequate alkalized before starting methotrexate
- Administer leucovorin rescue with doses greater than >500 mg/m2
- Glucarpidase can be administered as an antidote.
How does Glucarpidase work as a antidote with Methotrexate?
This drug works as follows when used as a Methotrexate antidote:
- Glucarpidase is an enzyme that hydrolyzes the methotrexate into inactive metabolites rapidly reducing the methotrexate concentration.
How is Glucarpidase given when used as a Methotrexate antidote?
This drug is given as follows when use as a Methotrexate rescue:
- The typical dose is 50 units/kg and it should ideally be given within 48-60 hours of methotrexate infusion (beyond this point, life threating toxicities may not be preventable).
Describe the strategy and rationale for management of dermatologic toxicity with Pemetrexed.
The strategy and rationale for management of this condition caused by this drug are:
- Pretreat with dexamethasone 4 mg orally twice daily for 3 days to reduce the incidence and severity of cutaneous reactions.
What are the clinical pearls of Methotrexate?
The clinical pearls of this drug are as follows:
- Most methotrexate protocols will require the urine pH to be >7 before starting methotrexate
- Doses >500 mg/m2 require leucovorin “rescue” and inpatient monitoring of levels to ensure appropriate methotrexate clearance
- High dose methotrexate may “third space” or accumulate in fluid collections leading to prolonged methotrexate clearance and increased toxicity. Patients with ascites. pericardial effusions. pleural effusions or other fluid collections should not receive high
dose methotrexate until those have been drained.
- Methotrexate has many drug interactions which can cause delayed clearance. Medications that must be stopped prior to high dose methotrexate include:
- Bactrim, PPIs, Penicillins, Salicylates, Probenecid, NSAIDs, Tetracyclines, and Ciprofloxacin.
- Many of these agents can be stopped 1-2 days prior to high dose methotrexate and can be resumed after adequate clearance.
- Intrathecal methotrexate or low oral doses of methotrexate do not have the same drug interaction concerns.
- When checking doses on oral methotrexate, only oncologic indications will have daily dosing options. If a prescription for lupus, psoriasis, arthritis, etc. is written for daily (instead of weekly) it’s likely an error!
What drugs must be stopped prior to high dose methotrexate?
Medications that must be stopped prior to administration of this drug include:
- Bactrim
- PPIs
- Penicillins
- Salicylates
- Probenecid
- NSAIDs
- Tetracyclines
- Ciprofloxacin
How does Leucovorin work as a “rescue” with Methotrexate?
This drug works as follows when used as a Methotrexate rescue:
- It is folinic acid (an active form of folate) that does not need to be processed by dihydrofolate reductase. It is given to rescue healthy cells from the toxicity of methotrexate and replenish the supply of folate metabolites depleted by methotrexate.
How is Leucovorin given when used as a Methotrexate rescue?
This drug is given as follows when use as a Methotrexate rescue:
- Usually started 12-24 hours post high dose methotrexate and given until serum methotrexate levels are below a certain threshold (often 0.05 mM).
- Dosing varies per protocol but oral absorption is saturable at doses >25 mg, so doses >25 mg are often given IV.
- Typical dosing frequency is orally every 6 hours, although dose and frequency may be increased if a patient is experiencing methotrexate toxicity.
What are the clinical pearls of Pemetrexed?
The clinical pearls of this drug are as follows:
- Patients receiving pemetrexed require vitamin supplementation with folic acid and B12.
- Give folic acid 400 to 1,000 mcg daily starting 7 days before initial pemetrexed dose and continue daily during treatment and for 21 days after last pemetrexed dose.
- Give Vitamin B12 1,000 mcg IM starting 7 days prior to treatment initiation and then every 3 cycles.
- To prevent dermatologic toxicity, pretreat with dexamethasone
- Patients with a CrCl 45 to 79 mL/min must avoid ibuprofen for 2 days before, the day of, and for 2 days following a dose of pemetrexed. Monitor more frequently for myelosuppression, renal dysfunction, and GI toxicities if concomitant Ibuprofen administration cannot be avoided.
What drugs are in the Hypomethylator class?
Drugs in this class are:
- Azacitidine
- Decitabine
What is the brand name of Azacitidine?
The brand name of this generic drug is:
- Vidaza (IV, SubQ)
- Onureg (Oral)
What is the brand name of Decitabine?
The brand name of this generic drug is:
- Dacogen
What is the generic of name of Vidaza?
The generic name of this brand name drug is:
- Azacitidine
What is the generic of name of Onureg?
The generic name of this brand name drug is:
- Azacitidine
What is the generic of name of Dacogen?
The generic name of this brand name drug is:
- Decitabine
What are the main indications for use of Azacitidine?
The main indications of this drug are:
- AML
- MDS
What are the main indications for use of Decitabine?
The main indications of this drug are:
- AML
- MDS
What are the main/common indications of the Hypomethylator class?
The main/common indications of this drug class are:
- AML
- MDS
What is the class and MOA of Azacitidine?
This drug in the following class:
- Hypomethylator
This drug’s MOA is as follows:
- Methylation (via methyltransferase) of tumor suppressor genes can contribute to the growth and survival of the cancer. Hypomethylating agents prevent DNA methylation by inhibiting methyltransferase, thus allowing for tumor suppressor gene expression which thus inhibits cancer growth.
What is the class and MOA of Decitabine?
This drug in the following class:
- Hypomethylator
This drug’s MOA is as follows:
- Methylation (via methyltransferase) of tumor suppressor genes can contribute to the growth and survival of the cancer. Hypomethylating agents prevent DNA methylation by inhibiting methyltransferase, thus allowing for tumor suppressor gene expression which thus inhibits cancer growth.
What is the emetic potential of Azacitidine?
The emetic potential of this drug is:
- Moderate
Describe the emetic potential of Decitabine.
The emetic potential of this drug is:
- Minimal
What drugs in the Hypomethylator class have a high emetic potential?
Drugs in the class with a high emetic potential are:
- None, N/A
What drugs in the Hypomethylator class have a moderate emetic potential?
Drugs in the class with a moderate emetic potential are:
- Azacitidine
What drugs in the Hypomethylator class have a low emetic potential?
Drugs in the class with a low emetic potential are:
- None, N/A
What drugs in the Hypomethylator class have a minimal emetic potential?
Drugs in the class with a minimal emetic potential are:
- Decitabine
Describe the extravasation risk and management strategies for Azacitidine.
The extravasation risk and management strategies for this drug are as follows:
- None, N/A
Describe the extravasation risk and management strategies for Decitabine.
The extravasation risk and management strategies for this drug are as follows:
- None, N/A
Describe the extravasation risk and management strategies for the Hypomethylator class.
The extravasation risk and management strategies for this drug class are as follows:
- None, N/A
Describe the distribution of the Hypomethylator class.
The distribution of this class is described as follows:
- Hypomethylating agents do not cross the blood brain barrier and will have limited utility in treating patients with central nervous system disease.
Describe the administration of Azacitidine.
The administration of this drug is described as follows:
- Vidaza is given IV or SubQ
- Onureg is given orally
What are the notable/common ADRs of the Hypomethylator class?
The notable/common ADRs of this drug class are:
- Bone marrow suppression
Describe the strategy and rationale for management of bone marrow suppression caused by hypomethylators.
The strategy and rationale for management of this condition caused by this drug are:
- This is the major side effect of the hypomethylators, however it can be difficult to determine if it is from the chemotherapy or the patient’s disease.
- In many cases, we will treat through it for the first few cycles of therapy (due to the long time to response of hypomethylators) but patients with this after 3-4 months of therapy may need a bone marrow biopsy to rule out relapsed disease.
What are the clinical pearls of the Hypomethylator class?
The clinical pearls of this drug class are as follows:
- When used as single agent therapy. hypomethylators have a median response time of 3-4 months.
- These agents are typically well tolerated and are a good choice of therapy for older/frail patients who may not be able to tolerate intensive chemotherapy.
- Recent data has shown that patients have improved response rates when combining hypomethylators with venetoclax (an oral BCL2 inhibitor).
- This combination also increases toxicity but is preferentially used in patients who can tolerate it.
What drugs are in the Platinum Analogue class?
Drugs in this class are:
- Carboplatin
- Cisplatin
- Oxaliplatin
What is the brand name of Carboplatin?
The brand name of this generic drug is:
- Paraplatin
What is the brand name of Cisplatin?
The brand name of this generic drug is:
- Platinol
What is the brand name of Oxaliplatin?
The brand name of this generic drug is:
- Eloxatin
What is the generic of name of Paraplatin?
The generic name of this brand name drug is:
- Carboplatin
What is the generic of name of Platinol?
The generic name of this brand name drug is:
- Cisplatin
What is the generic of name of Eloxatin?
The generic name of this brand name drug is:
- Oxaliplatin
What are the main indications for use of Carboplatin?
The main indications of this drug are:
- Anal Cancer
- Bladder Cancer
- Breast Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancer
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- NSCLC
- SCLC
- Gynecologic Cancer
- Testicular Cancer
What are the main indications for use of Cisplatin?
The main indications of this drug are:
- Anal Cancer
- Bladder Cancer
- Breast Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancer
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- NSCLC
- SCLC
- Gynecologic Cancer
- Testicular Cancer
What are the main indications for use of Oxaliplatin?
The main indications of this drug are:
- Esophageal Cancer
- Gastric Cancer
- Non-Hodgkin Lymphoma
- Testicular Cancer
- Biliary Adencocarcinoma
- Colorectal Cancer
- Pancreatic Cancer
What is the class and MOA of Carboplatin?
This drug in the following class:
- Platinum Analogues
This drug’s MOA is as follows:
- Alkylating agents which covalently binds to DNA and interfere with the function of DNA by producing interstrand DNA cross-links.
- They preferentially bind to the N-7 position of guanine.
What is the class and MOA of Cisplatin?
This drug in the following class:
- Platinum Analogues
This drug’s MOA is as follows:
- Alkylating agents which covalently binds to DNA and interfere with the function of DNA by producing interstrand DNA cross-links.
- They preferentially bind to the N-7 position of guanine.
What is the class and MOA of Oxaliplatin?
This drug in the following class:
- Platinum Analogues
This drug’s MOA is as follows:
- Alkylating agents which covalently binds to DNA and interfere with the function of DNA by producing interstrand DNA cross-links.
- They preferentially bind to the N-7 position of guanine.
What are the notable monitoring parameters for the Platinum Analogues?
The notable monitoring parameters for this drug class are:
- S/Sx of nephrotoxicity - renal panel
- S/Sx of ototoxicity - consider audiometric and vestibular testing, particularly in all pediatric patients receiving cisplatin (pediatric patients should receive audiometric testing at baseline, prior to each dose, and for several years after discontinuing therapy).
- S/Sx of neuropathy - neurologic evaluation prior to each dose and periodically thereafter
What is the emetic potential of Carboplatin?
The emetic potential of this drug is:
- High if AUC >4
- Moderate if AUC <4
What is the emetic potential of Cisplatin?
The emetic potential of this drug is:
- High (commonly regarded as the most emetogenic of all chemotherapies)
What is the emetic potential of Oxaliplatin?
The emetic potential of this drug is:
- Moderate
Describe the emetic potential of the Platinum Analogues.
The emetic potential of this drug class is:
- Moderate (Oxaliplatin, Carboplatin AUC <4) to High (Carboplatin AUC >4, Cisplatin)
What drugs in the Platinum Analogue class have a high emetic potential?
Drugs in the class with a high emetic potential are:
- Cisplatin (commonly regarded as the most emetogenic of all chemotherapies)
- Carboplatin if AUC >4
What drugs in the Platinum Analogue class have a moderate emetic potential?
Drugs in the class with a moderate emetic potential are:
- Carboplatin if AUC <4
- Oxaliplatin
What drugs in the Platinum Analogue class have a low emetic potential?
Drugs in the class with a low emetic potential are:
- None, N/A
What drugs in the Platinum Analogue class have a minimal emetic potential?
Drugs in the class with a minimal emetic potential are:
- None, N/A
Describe the extravasation risk and management strategies for Oxaliplatin.
The extravasation risk and management strategies for this drug are as follows:
- Irritant with vesicant- like properties
- If extravasation occurs, stop infusion and aspirate. Data conflicts regarding use of warm or cold compresses
- Cold compresses may reduce cellulary injury but could potentially precipitate or exacerbate peripheral neuropathy
- Warm compresses may increase local drug removal but may increase cellular uptake and injury
Describe the extravasation risk and management strategies for the Platinum Analogue class.
The extravasation risk and management strategies for this drug class are as follows:
- Carboplatin may be an irritant
- Cisplatin is a vesicant at higher concentrations
- Oxaliplatin is irritant with vesicant like properties
Describe the metabolism of the Platinum Analogues.
The metabolism of this drug is as follows:
- Clearance is renal
- The mean AUC of unbound platinum increases as renal function decreases
- 40% increase with mild (CrCl 50 to 80 ml /minute) renal impairment
- 95% increase with moderate (CrCl 30 to 49 ml /minute) renal impairment
- 342% increase with severe (CrCl <30 ml /minute) renal impairment
What are the notable ADRs of Carboplatin?
The notable ADRs of this drug are:
- Chronic Peripheral Neuropathy
- Nephrotoxicity
- Hypersensitivity Reactions
What are the notable ADRs of Cisplatin?
The notable ADRs of this drug are:
- Ototoxicity
- Chronic Peripheral Neuropathapy
- Nephrotoxicity
- Hypersensitivity Reactions
What are the notable ADRs of Oxaliplatin?
The notable ADRs of this drug are:
- Chronic Peripheral Neuropathapy
- Acute Peripheral Neuropathy (unique to oxaliplatin vs other platinums)
- Nephrotoxicity
- Hypersensitivity Reactions
What are the notable/common ADRs of the Platinum Analogue class?
The notable/common ADRs of this drug class are:
- Chronic Peripheral Neuropathy (acute is unique to oxaliplatin)
- Nephrotoxicity
- Ototoxicity (cisplatin)
- Hypersensitivity Reactions (especially carboplatin and oxaliplatin)
What drug(s) of the Platinum Analogue class is notable for causing electrolyte wasting?
The drugs in this class notable for cause this condition are:
- All can but it is especially notable for Cisplatin
What drug(s) of the Platinum Analogue class is notable for causing ototoxicity?
The drugs in this class notable for cause this condition are:
- Cisplatin (especially in children and even moreso in pediatrics)
What drug(s) of the Platinum Analogue class is notable for causing acute peripheral neuropathy?
The drugs in this class notable for cause this condition are:
- Oxaliplatin
What drug(s) of the Platinum Analogue class is notable for causing hypersensitivity reactions?
The drugs in this class notable for cause this condition are:
- All can but it is especially notable for Carboplatin and Oxaliplatin
Describe the strategy and rationale for management of Peripheral Neuropathy caused by Platinum Analogues.
The strategy and rationale for management of this condition caused by this drug class are:
- This can be broken down into two types: acute and chronic
- Chronic mimics traditional peripheral neuropathy with numbness/tingling in the fingers and toes.
- This can occur >14 days after the dose.
- Can be persistent and interfere with daily activities like writing or walking.
- Symptoms may improve in some patients upon discontinuing treatment.
- Acute is unique to oxaliplatin and presents as cold-induced neuropathy.
- Often occurs within hours of the oxaliplatin infusion and resolves within 7 days.
- Symptoms may include transient paresthesia, dysesthesia, and hypoesthesia (in the hands, feet, perioral area, or throat), jaw spasm, abnormal tongue sensation, or a feeling of chest pressure.
- Patients should be counseled to avoid ice chips, exposure to cold temperatures, and cold food/beverages during or within hours after oxaliplatin infusion.
Describe the strategy and rationale for management of nephrotoxicity caused by Platinum Analogues.
The strategy and rationale for management of this condition caused by this drug class are:
- All of the platinum agents have the potential to cause nephrotoxicity.
- Patients should receive aggressive pre and post platinum hydration with normal saline, ideally targeting urine output of 100 ml/hour prior to the chemotherapy infusion.
- Patients also should receive potassium and magnesium replacement as these agents (especially cisplatin) can cause electrolyte wasting.
Describe the strategy and rationale for management of ototoxicity caused by Platinum Analogues.
The strategy and rationale for management of this condition caused by this drug class are:
- Cisplatin may cause cumulative and severe ototoxicity.
- Manifested by tinnitus, high-frequency (4,000 to 8,000 Hz) hearing loss, and/or decreased ability to hear normal conversational tones.
- May occur during or after treatment and may be unilateral or bilateral.
- More common in children and even moreso in pediatrics (40%-60%).
- Consider audiometric and vestibular testing, particularly in all pediatric patients receiving cisplatin.
Describe the strategy and rationale for management of hypersensitivity reactions caused by Platinum Analogues.
The strategy and rationale for management of this condition caused by this drug class are:
- Platinum agents are the second most common source of hypersensitivity reactions among chemotherapy agents (following asparaginase products).
- Especially common with Carboplatin and Oxaliplatin
- For Carboplatin:
- The incidence of carboplatin hypersensitivity reactions is between 1-44%.
- Most common after 6 -8 doses
- Patients with mild-moderate reactions can be desensitized and may continue to receive infusions
- For Oxaliplatin:
- The incidence of acute reactions is between 12-25% with up to 30% of those being severe infusion reactions.
- Reactions may occur within minutes of drug administration and with any cycle
- Similar to carboplatin, the risk of hypersensitivity reaction is higher with multiple cycles of therapy.
- Patients with mild reactions may be re-challenged.
What are the clinical pearls of Carboplatin?
The clinical pearls of this drug are as follows:
- Dosing is based off target AUC (usually 2-6)
Describe the use of the Calvert formula.
This use of this formula is as follows:
- Used to calculate Carboplatin dose using target AUC
- Total dose (mg) = Target AUC x (GFR + 25)
- If estimating instead of measuring GFR (as with Cockroft Gault), protocols typically cap GFR at a maximum of 125 ml/minute to avoid potential toxicity (although this does vary per indication)
What are the clinical pearls of the Platinum Analogue class?
The clinical pearls of this drug class are as follows:
- They are the second most common source of hypersensitivity reactions among chemotherapy agents (following asparaginase products).
What drugs are in the Purine Antagonist class?
Drugs in this class are:
- 6-Mercatopurine (6-MP)
- Fludarabine
- Cladribine
- Clofarabine
- Nelarabine
- Pentostatin
- Thioguanine
What is the brand name of 6Mercatopurine (6MP)?
The brand name of this generic drug is:
- Purixan
What is the brand name of Fludarabine?
The brand name of this generic drug is:
- Fludara
What is the brand name of Cladribine?
The brand name of this generic drug is:
- Mavenclad
- Leustatin
What is the brand name of Clofarabine?
The brand name of this generic drug is:
- Clolar
- Clofarex
What is the brand name of Nelarabine?
The brand name of this generic drug is:
- Arranon
What is the brand name of Pentostatin?
The brand name of this generic drug is:
- Nipent
What is the brand name of Thioguanine?
The brand name of this generic drug is:
- Nipent
What is the generic of name of Purixan?
The generic name of this brand name drug is:
- 6Mercatopurine
What is the generic of name of Fludara?
The generic name of this brand name drug is:
- Fludarabine
What is the generic of name of Mavenclad?
The generic name of this brand name drug is:
- Cladribine
What is the generic of name of Clolar?
The generic name of this brand name drug is:
- Clofarabine
What is the generic of name of Arranon?
The generic name of this brand name drug is:
- Nelarabine
What is the generic of name of Nipent?
The generic name of this brand name drug is:
- Pentostatin
What is the generic of name of Nipent?
The generic name of this brand name drug is:
- Thioguanine
What are the main indications for use of 6Mercatopurine?
The main indications of this drug are:
- ALL
What are the main indications for use of Fludarabine?
The main indications of this drug are:
- CLL
- AML
- HSCT
- Non-Hodkin Lymphoma
What are the main/common indications of the Purine Antagonist class?
The main/common indications of this drug class are:
- Leukemias with Fludarabine
- Non-Hodgkin Lymphoma with 6MP
What is the class and MOA of 6Mercaptopurine?
This drug in the following class:
- Purine Antagonist
This drug’s MOA is as follows:
- Purine antagonists inhibit DNA and RNA synthesis by acting as false metabolite.
- The anti-metabolite is incorporated into DNA and RNA eventually inhibiting the ir synthesis.
- They are specific for the S phase of the cell cycle.
What is the class and MOA of Fludarabine?
This drug in the following class:
- Purine Antagonist
This drug’s MOA is as follows:
- Purine antagonists inhibit DNA and RNA synthesis by acting as false metabolite.
- The anti-metabolite is incorporated into DNA and RNA eventually inhibiting the ir synthesis.
- They are specific for the S phase of the cell cycle.
What is the class and MOA of Cladribine?
This drug in the following class:
- Purine Antagonist
This drug’s MOA is as follows:
- Purine antagonists inhibit DNA and RNA synthesis by acting as false metabolite.
- The anti-metabolite is incorporated into DNA and RNA eventually inhibiting the ir synthesis.
- They are specific for the S phase of the cell cycle.
What is the class and MOA of Clofarabine?
This drug in the following class:
- Purine Antagonist
This drug’s MOA is as follows:
- Purine antagonists inhibit DNA and RNA synthesis by acting as false metabolite.
- The anti-metabolite is incorporated into DNA and RNA eventually inhibiting the ir synthesis.
- They are specific for the S phase of the cell cycle.
What is the class and MOA of Nelarabine?
This drug in the following class:
- Purine Antagonist
This drug’s MOA is as follows:
- Purine antagonists inhibit DNA and RNA synthesis by acting as false metabolite.
- The anti-metabolite is incorporated into DNA and RNA eventually inhibiting the ir synthesis.
- They are specific for the S phase of the cell cycle.
What is the class and MOA of Pentostatin?
This drug in the following class:
- Purine Antagonist
This drug’s MOA is as follows:
- Purine antagonists inhibit DNA and RNA synthesis by acting as false metabolite.
- The anti-metabolite is incorporated into DNA and RNA eventually inhibiting the ir synthesis.
- They are specific for the S phase of the cell cycle.
What is the class and MOA of Thioguanine?
This drug in the following class:
- Purine Antagonist
This drug’s MOA is as follows:
- Purine antagonists inhibit DNA and RNA synthesis by acting as false metabolite.
- The anti-metabolite is incorporated into DNA and RNA eventually inhibiting the ir synthesis.
- They are specific for the S phase of the cell cycle.
What is the emetic potential of 6Mercatopurine?
The emetic potential of this drug is:
- Minimal to Low
What is the emetic potential of Fludarabine?
The emetic potential of this drug is:
- Minimal
Describe the emetic potential of the Purine Antagonist class.
The emetic potential of this drug class is:
- Minimal to Low except for Clofarabine (Moderate)
What drugs in the Purine Antagonist class have a high emetic potential?
Drugs in the class with a high emetic potential are:
- None, N/A
What drugs in the Purine Antagonist class have a moderate emetic potential?
Drugs in the class with a moderate emetic potential are:
- Clofarabine
What drugs in the Purine Antagonist class have a low emetic potential?
Drugs in the class with a low emetic potential are:
- All are Minimal to Low except for:
- Fludarabine and Cladribine (Minimal)
- Clofarabine (Moderate)
What drugs in the Purine Antagonist class have a minimal emetic potential?
Drugs in the class with a minimal emetic potential are:
- Fludarabine
- Cladribine
- All the rest are “Minimal to Low” except for Clofarabine (Moderate)
Describe the extravasation risk and management strategies for the Purine Antagonist class.
The extravasation risk and management strategies for this drug class are as follows:
- None, N/A
Describe the metabolism of 6Mercaptopurine.
The metabolism of this drug is as follows:
- Total body clearance of the principal metabolite correlates with creatinine clearance
Describe the metabolism of Fludarabine.
The metabolism of this drug is as follows:
- Renal impairment may result in slower elimination of parent drug and metabolite, and a greater cumulative effect
What are the clinical pearls of 6Mercaptopurine?
The clinical pearls of this drug are as follows:
- Doses for ALL are typically titrated to maintain an ANC between 500-1500 cells/mcL. Methods of dose titration will vary per protocol but typically involve adjusting doses every 4-8 weeks.
- In patients intolerant to this drug (abnormally low CBC unresponsive to dose reduction, severe bone marrow toxicities, or repeated myelosuppressive episodes), consider genotyping of NUDT15 and TPMT.
- NUDT15 and TPMT genotyping or phenotyping may assist in identifying patients at risk for developing toxicity and those who may needs empiric dose reductions due to decreased metabolism of 6-MP.
What drugs are in the Pyrimidine Antagonist class?
Drugs in this class are:
- Gemcitabine
- 5Fluorouracil (5FU)
- Capecitabine
- Cytarabine
- Floxuridine
What is the brand name of Gemcitabine?
The brand name of this generic drug is:
- Infugem
- Gemzar
What is the brand name of 5Fluorouracil?
The brand name of this generic drug is:
- Adrucil
What is the brand name of Capecitabine?
The brand name of this generic drug is:
- Xeloda
What is the brand name of Cytarabine?
The brand name of this generic drug is:
- AraC
- Cytosar
What is the brand name of Floxuridine?
The brand name of this generic drug is:
- Fluorouridine deoxyribose
What is the generic of name of Infugem?
The generic name of this brand name drug is:
- Gemcitabine
What is the generic of name of Gemzar?
The generic name of this brand name drug is:
- Gemcitabine
What is the generic of name of Adrucil?
The generic name of this brand name drug is:
- 5Fluorouracil
What is the generic of name of Xeloda?
The generic name of this brand name drug is:
- Capecitabine
What is the generic of name of AraC?
The generic name of this brand name drug is:
- Cytarabine
What is the generic of name of Cytosar?
The generic name of this brand name drug is:
- Cytarabine
What is the generic of name of Fluorouridine deoxyribose?
The generic name of this brand name drug is:
- Floxuridine
What are the main indications for use of Gemcitabine?
The main indications of this drug are:
- Breast Cancer
- Head and Neck Cancers
- Pancreatic Cancer
- Bladder Cancer
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- Small Cell Lung Cancer
- Non-Small Cell Lung Cancer
What are the main indications for use of 5Fluorouracil?
The main indications of this drug are:
- Anal Cancer
- Breast Cancer
- Colorectal Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancers
- Pancreatic Cancer
What are the main indications for use of Capecitabine?
The main indications of this drug are:
- Anal Cancer
- Breast Cancer
- Colorectal Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancers
- Pancreatic Cancer
What is the class and MOA of Gemcitabine?
This drug in the following class:
- Pyrimidine Antagonist
This drug’s MOA is as follows:
- It interferes with DNA and RNA synthesis due to structural similarity to pyrimidine.
- The antimetabolite is substituted for normal building blocks of RNA/DNA and interferes with enzyme activity causing cell death.
What is the class and MOA of 5Fluorouracil?
This drug in the following class:
- Pyrimidine Antagonist
This drug’s MOA is as follows:
- It interferes with DNA and RNA synthesis due to structural similarity to pyrimidine.
- The antimetabolite is substituted for normal building blocks of RNA/DNA and interferes with enzyme activity causing cell death.
- After activation, F-UMP (an active metabolite) is incorporated into RNA to replace uracil and inhibit cell growth
- The active metabolite F-dUMP inhibits thymidylate synthetase
What is the class and MOA of Capecitabine?
This drug in the following class:
- Pyrimidine Antagonist
This drug’s MOA is as follows:
- Capecitabine is a prodrug of fluorouracil.
- It interferes with DNA and RNA synthesis due to structural similarity to pyrimidine.
- The antimetabolite is substituted for normal building blocks of RNA/DNA and interferes with enzyme activity causing cell death.
- After activation of Fluorouracil, F-UMP (an active metabolite) is incorporated into RNA to replace uracil and inhibit cell growth
- The active metabolite F-dUMP inhibits thymidylate synthetase
What is the class and MOA of Cytarabine?
This drug in the following class:
- Pyrimidine Antagonist
This drug’s MOA is as follows:
- Cytarabine is a pyrimidine analog and is incorporated into DNA; however, the primary action is inhibition of DNA polymerase resulting in decreased DNA synthesis and repair.
What is the class and MOA of Floxuridine?
This drug in the following class:
- Pyrimidine Antagonist
This drug’s MOA is as follows:
- It is catabolized to fluorouracil after intra-arterial administration, resulting in activity similar to fluorouracil
- It inhibits thymidylate synthetase
- It interferes with DNA and RNA synthesis due to structural similarity to pyrimidine.
- The antimetabolite is substituted for normal building blocks of RNA/DNA and interferes with enzyme activity causing cell death.
What are the notable monitoring parameters for 5Fluorouracil?
The notable monitoring parameters for this drug are:
- Monitor INR closely if patients are receiving concomitant warfarin therapy due to a drug-drug interaction.
What are the notable monitoring parameters for Capecitabine?
The notable monitoring parameters for this drug are:
- Monitor INR closely if patients are receiving concomitant warfarin therapy due to a drug-drug interaction.
What are the notable/common monitoring parameters for the Pyrimidine Antagonist class?
The notable/common monitoring parameters for this drug class are:
- Monitor INR closely if patients are receiving concomitant warfarin therapy and 5Fluorouracil or Capecitabine due to a drug-drug interaction.
What drug(s) notably require monitoring of INR if on concomitant warfarin therapy?
Drug(s) notably requiring this monitoring are:
- 5Fluorouracil
- Capecitabine
What is the emetic potential of 5Fluorouracil?
The emetic potential of this drug is:
- Low
What is the emetic potential of Capecitabine?
The emetic potential of this drug is:
- Low
What is the emetic potential of Gemcitabine?
The emetic potential of this drug is:
- Low
What is the emetic potential of Cytarabine?
The emetic potential of this drug is:
- Adults:
- Moderate if >1,000 mg/m2
- Low if ≤1,000 mg/m2
- Pediatrics:
- High if ≥3,000 mg/m2/day: High (>90%).
- Moderate for 75 mg/m2/dose.
Describe the emetic potential of the Pyrimidine Antagonist class.
The emetic potential of this drug class is:
- Low (except for Cytarabine*)
Describe the extravasation risk and management strategies for the Pyrimidine Antagonist class.
The extravasation risk and management strategies for this drug class are as follows:
- Fluorouracil may be an irritant. avoid extravasation.
Describe the administration of 5Fluorouracil.
The administration of this drug is described as follows:
- 5-FU is given as a 46-hour continuous infusion with some chemotherapy regimens.
- In these cases, leucovorin is often given to enhance the mechanism of 5-FU by adding additional inhibition of thymidylate synthase. This leads to increased cancer cell death but can also cause increased toxicities.
Describe the administration of Capecitabine.
The administration of this drug is described as follows:
- It is given orally often in divided doses, 12 hours apart, for 2 weeks on and 1 week off.
- It should be taken with food.
- Oral administration is similar to continuous infusion 5-FU in terms of toxicity.
Describe the administration of Floxuridine.
The administration of this drug is described as follows:
- Administered as a continuous hepatic intra-arterial infusion using an infusion pump.
Describe the metabolism of 5Fluorouracil.
The metabolism of this drug is as follows:
- HEPATICALLY metabolized to form active metabolites. 5-fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-
2’-deoxyuridine-5’-0 -monophosphate (F-dUMP)
Describe the metabolism of Capecitabine.
The metabolism of this drug is as follows:
- Enzymatically metabolized to fluorouracil.
Describe the metabolism of Gemcitabine.
The metabolism of this drug is as follows:
- Metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside metabolites
Describe the metabolism of Cytarabine.
The metabolism of this drug is as follows:
- Primarily hepatic
- Metabolized by deoxycytidine kinase to aracytidine triphosphate (active)
- ~90% of dose is metabolized to inactive uracil arabinoside (ARA-U); intrathecal administration results in little conversion to ARA-U due to the low levels of deaminase in the cerebral spinal fluid.
What are the notable ADRs of 5Fluorouracil?
The notable ADRs of this drug are:
- Hand-foot syndrome, also called palmar-plantar erythrodysesthesia. Patients can experience redness, swelling, and pain on the palms of the hands and/or the soles of the feet.
- A bolus dose of 5-FU is associated with myelosuppression while the continuous infusion 5-FU/capecitabine is more likely to cause diarrhea and hand/foot syndrome.
What are the notable ADRs of Capecitabine?
The notable ADRs of this drug are:
- Hand-foot syndrome, also called palmar-plantar erythrodysesthesia. Patients can experience redness, swelling, and pain on the palms of the hands and/or the soles of the feet.
What are the notable ADRs of Cytarabine?
The notable ADRs of this drug are:
- Cytarabine syndrome which is almost flu-like and is characterized by fever, myalgia, bone pain, chest pain (occasionally), maculopapular rash, conjunctivitis, and malaise.
- Occurs in up to 1/3rd of patients receiving Cytarabine for AML (most of whom have had prior exposure to the drug)
- It generally occurs 6 to 12 hours following administration.
What are the notable/common ADRs of the Pyrimidine Antagonist class?
The notable/common ADRs of this drug class are:
- Hand/Foot Syndrome (especially 5Fluorouracil and Capecitabine)
What drug(s) of the Pyrimidine Antagonist class is notable for causing Hand/Foot Syndrome?
The drugs in this class notable for cause this condition are:
- 5Fluorouracil and Capecitabine (and to a lesser degree Cytarabine)
Describe the strategy and rationale for management of intolerability to 5Fluorouracil.
The strategy and rationale for management of this condition caused by this drug are:
- Leucovorin is often given to enhance the mechanisam of 5-FU by adding additional inhibition of thymidylate synthase. This leads to increased cancer cell death but can also cause increased toxicities.
- In patients who are poorly tolerating their 5-FU/leucovorin containing regimens. you may consider omitting the leucovorin (instead of decreasing the 5-FU dose)
Describe the strategy and rationale for management of Hand/Foot Syndrome caused by 5Fluorouracil/Capecitabine.
The strategy and rationale for management of this condition caused by this drug are:
- It is thought to be caused by damage to the deep capillaries, leading to COX inflammatory-type reactions or related to enzymes involved in 5-FU metabolism
- It can be prevented by avoiding friction causing activities (lifting weights, running), avoiding hot water or other sources of heat, and using lotions or creams to keep skin moist.
- It is treated by holding chemotherapy, and applying topical or oral anti-inflammatory agents and analgesics.
Describe the strategy and rationale for management of Cytarabine Syndrome.
The strategy and rationale for management of this condition caused by this drug are:
- While the etiology is unclear, it is probably related to cytokine release rather than immune-mediated
- Acetaminophen before and after dose may reduce the frequency of the cytarabine syndrome.
- Glucocorticoids may also be beneficial for both treatment and prevention of the cytarabine syndrome.
- Retreatment after Cytarabine syndrome can usually be safely accomplished with increased premedication, even in patients with multiple reactions
What are the clinical pearls of Capecitabine?
The clinical pearls of this drug are as follows:
- Oral capecitabine has many drug interactions to be aware of including:
- PPIs (which can decrease efficacy)
- Warfarin (increased INR)
What drugs are in the Taxanes class?
Drugs in this class are:
- Docetaxel
- Cabazitaxel
- Paclitaxel
- NabPaclitaxel
What is the brand name of Docetaxel?
The brand name of this generic drug is:
- Taxotere
What is the brand name of Cabazitaxel?
The brand name of this generic drug is:
- Jevtana
What is the brand name of Paclitaxel?
The brand name of this generic drug is:
- Taxol
What is the brand name of NabPaclitaxel?
The brand name of this generic drug is:
- Abraxane
What is the generic of name of Taxotere?
The generic name of this brand name drug is:
- Docetaxel
What is the generic of name of Jevtana?
The generic name of this brand name drug is:
- Cabazitaxel
What is the generic of name of Taxol?
The generic name of this brand name drug is:
- Paclitaxel
What is the generic of name of Abraxane?
The generic name of this brand name drug is:
- NabPaclitaxel
What are the main indications for use of Docetaxel?
The main indications of this drug are:
- Breast Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancer
- Non-Small Cell Lung Cancer
- Ovarian Cancer
- Prostate Cancer
- Small Cell Lung Cancer
What are the main indications for use of Paclitaxel?
The main indications of this drug are:
- Breast Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancer
- Non-Small Cell Lung Cancer
- Ovarian Cancer
- Small Cell Lung Cancer
- Anal Cancer
- Bladder Cancer
- Cervical Cancer
- Endometrial Cancer
- Kaposi Sarcoma
What are the main indications for use of NabPaclitaxel?
The main indications of this drug are:
- Breast Cancer
- Non-Small Cell Lung Cancer
- Ovarian Cancer
- Bladder Cancer
- Cervical Cancer
- Biliary Cancer
- Pancreatic Cancer
What is the class and MOA of Docetaxel?
This drug in the following class:
- Taxanes
This drug’s MOA is as follows:
- Taxanes inhibit the mitotic spindle.
- They bind to tubulin and prevent microtubule depolymerization - therefore inhibiting mitosis and inducing apoptosis in cells undergoing the division process.
- These drugs are cell-cycle specific in the M-phase.
What is the class and MOA of Cabazitaxel?
This drug in the following class:
- Taxanes
This drug’s MOA is as follows:
- Taxanes inhibit the mitotic spindle.
- They bind to tubulin and prevent microtubule depolymerization - therefore inhibiting mitosis and inducing apoptosis in cells undergoing the division process.
- These drugs are cell-cycle specific in the M-phase
- Unlike other taxanes, this drug has a poor affinity for multidrug resistance (MDR) proteins, therefore conferring activity in resistant tumors.
What is the class and MOA of Paclitaxel?
This drug in the following class:
- Taxanes
This drug’s MOA is as follows:
- Taxanes inhibit the mitotic spindle.
- They bind to tubulin and prevent microtubule depolymerization - therefore inhibiting mitosis and inducing apoptosis in cells undergoing the division process.
- These drugs are cell-cycle specific in the M-phase.
What is the class and MOA of NabPaclitaxel?
This drug in the following class:
- Taxanes
This drug’s MOA is as follows:
- Taxanes inhibit the mitotic spindle.
- They bind to tubulin and prevent microtubule depolymerization - therefore inhibiting mitosis and inducing apoptosis in cells undergoing the division process.
- These drugs are cell-cycle specific in the M-phase.
Describe the emetic potential of the Taxanes class.
The emetic potential of this drug class is:
- Low (all agents)
Describe the extravasation risk and management strategies for Paclitaxel.
The extravasation risk and management strategies for this drug are as follows:
- Irritant with vesicant-like properties
- Consider the use of hyaluronidase - Administer 1 to 6 ml (150 units/ml) into existing IV line: usual dose is 1 ml for each 1 ml of extravasated drug.
Describe the extravasation risk and management strategies for Docetaxel.
The extravasation risk and management strategies for this drug are as follows:
- Irritant with vesicant-like properties
Describe the extravasation risk and management strategies for the Taxanes class.
The extravasation risk and management strategies for this drug class are as follows:
- Paclitaxel and Docetaxel are irritants with vesicant-like properties
- NabPaclitaxel may be an irritant
Describe the administration of Docetaxel.
The administration of this drug is described as follows:
- Use Low-sorb tubing BUT NO IN-LINE FILTER
Describe the administration of Cabazitaxel.
The administration of this drug is described as follows:
- Use Low-sorb tubing with an in-line filter
Describe the administration of Paclitaxel.
The administration of this drug is described as follows:
- Use Low-sorb tubing with an in-line filter
Describe the general techniques for administration of the Taxanes class.
The general techniques for administration of this drug class is described as follows:
- Paclitaxel and Cabazitaxel require low-sorb tubing and in-line filter
- Docetaxel requires low-sorb tubing BUT NO IN-LINE FILTER
Describe the metabolism of Docetaxel.
The metabolism of this drug is as follows:
- Primarily hepatic metabolism by CYP3A4 (CYP2C8 minor).
- Dose adjustments are recommended in patients with hepatic impairment.
Describe the metabolism of Cabazitaxel.
The metabolism of this drug is as follows:
- Primarily hepatic metabolism by CYP3A4/3A5 (CYP2C8 minor).
- Dose adjustments are recommended in patients with hepatic impairment.
Describe the metabolism of Paclitaxel.
The metabolism of this drug is as follows:
- Primarily hepatic metabolism by CYP2C8 (CYP3A4 minor).
- Dose adjustments are recommended in patients with hepatic impairment.
Describe the metabolism of NabPaclitaxel.
The metabolism of this drug is as follows:
- Primarily hepatic metabolism by CYP2C8 (CYP3A4 minor).
- Dose adjustments are recommended in patients with hepatic impairment.
What are the notable ADRs of Paclitaxel?
The notable ADRs of this drug are:
- Infusion reactions
What are the notable ADRs of Docetaxel?
The notable ADRs of this drug are:
- Peripheral edema (black box warning)
Describe the strategy and rationale for management of infusion reactions caused by Paclitaxel.
The strategy and rationale for management of this condition caused by this drug are:
- This drug has poor water solubility and is thus formulated with a polyethoxylated castor oil (Cremophor).
- This viscous solution is likely to cause hypersensitivity reactions, but these reactions are due to the Cremophor (not the drug itself).
- In order to prevent these reactions, patients should be premedicated with antihistamines and corticosteroids. Typically, patients receive dexamethasone 10-20 mg oral 12 and 6 hours prior to the infusion, plus diphenhydramine 50 mg IV and ranitidine 50 mg IV 30 minutes prior to the infusion.
Describe the strategy and rationale for management of peripheral edema caused by Docetaxel.
The strategy and rationale for management of this condition caused by this drug are:
- Characterized by pleural effusions (requiring immediate drainage), ascites with pronounced abdominal distention, peripheral edema, dyspnea at rest, cardiac tamponade, and/or generalized edema.
- Premedication with corticosteroids for 3 days, beginning the day before drug administration, is recommended to prevent pulmonary/peripheral edema.
- Patients typically receive dexamethasone 8mg oral twice daily 1 day prior to drug and continuing for 2 days after.
What are the clinical pearls of NabPaclitaxel?
The clinical pearls of this drug are as follows:
- Not interchangeable with other paclitaxel formulations and cannot be substituted for conventional paclitaxel.
What is the history of the Taxanes class?
The history of this drug class is as follows:
- Discovered in 1971 by NCI researchers during a plant screening program when a crude extract with anti-tumor activity was isolated from the bark of the Pacific Yew, Taxus brevifolia.
- But the amount of paclitaxel in yew bark was small and extracting it was complicated and expensive and the collection of Pacific Yew bark also became restricted for environmental reasons.
- This led to production of semi-synthetic form of paclitaxel derived from the needles of the Himalayan yew tree, Taxus bacatta.
What drug(s) of the Taxanes class is notable for causing Peripheral Edema?
The drugs in this class notable for cause this condition are:
- Docetaxel
What drug(s) of the Taxanes class is notable for causing Infusion Reactions?
The drugs in this class notable for cause this condition are:
- Paclitaxel (due to Cremophor)
What drugs are in the Topoisomerase Inhibitors class?
Drugs in this class are:
- lrinotecan
- Topotecan
- Etoposide
- Teniposide
- Mitoxantrone
What is the brand name of lrinotecan?
The brand name of this generic drug is:
- Camptosar
What is the brand name of Topotecan?
The brand name of this generic drug is:
- Hycamtin
What is the brand name of Etoposide?
The brand name of this generic drug is:
- Toposar, Vepesid, VP16
What is the brand name of Teniposide?
The brand name of this generic drug is:
- VM26
What is the brand name of Mitoxantrone?
The brand name of this generic drug is:
- Novantrone
What is the generic of name of Camptosar?
The generic name of this brand name drug is:
- lrinotecan
What is the generic of name of Hycamtin?
The generic name of this brand name drug is:
- Topotecan
What is the generic of name of Toposar?
The generic name of this brand name drug is:
- Etoposide
What is the generic of name of Vepesid?
The generic name of this brand name drug is:
- Etoposide
What is the generic of name of VP16?
The generic name of this brand name drug is:
- Etoposide
What is the generic of name of VM26?
The generic name of this brand name drug is:
- Teniposide
What is the generic of name of Novantrone?
The generic name of this brand name drug is:
- Mitoxantrone
What are the main indications for use of lrinotecan?
The main indications of this drug are:
- Non-Small Cell Lung Cancer
- Small Cell Lung Cancer
- Colorectal Cancer
- Esophageal Cancer
- Gastric Cancer
- Pancreatic Cancer
What are the main indications for use of Topotecan?
The main indications of this drug are:
- Small Cell Lung Cancer
- Cervical Cancer
- CNS Malignancy
- Ewing Sarcoma
- Ovarian Cancer
- Rhabdomyosarcoma
What are the main indications for use of Etoposide?
The main indications of this drug are:
- Breast Cancer
- Hematopoietic Stem Cell Transplant
- Hemophagocytic Lymphohistiocytosis
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- Non-Small Cell Lung Cancer
- Small Cell Lung Cancer
- Testicular Cancer
What is the class and MOA of lrinotecan?
This drug in the following class:
- Topoisomerase I Inhibitors
This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase I introduces single stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.
What is the class and MOA of Topotecan?
This drug in the following class:
- Topoisomerase I Inhibitors
This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase I introduces single stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.
What is the class and MOA of Etoposide?
This drug in the following class:
- Topoisomerase II Inhibitors (Podophyllotoxin Derivative)
This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase II introduces double stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.
What is the class and MOA of Teniposide?
This drug in the following class:
- Topoisomerase II Inhibitors (Podophyllotoxin Derivative)
This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase II introduces double stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.
What is the class and MOA of Mitoxantrone?
This drug in the following class:
- Topoisomerase II Inhibitors (Anthracenedione)
This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase II introduces double stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.
What is the emetic potential of Etoposide?
The emetic potential of this drug is:
- Low
What is the emetic potential of Topotecan?
The emetic potential of this drug is:
- Low
What is the emetic potential of Irinotecan?
The emetic potential of this drug is:
- Moderate
What is the emetic potential of Teniposide?
The emetic potential of this drug is:
- Low
What is the emetic potential of Mitoxantrone?
The emetic potential of this drug is:
- Low
Describe the emetic potential of the Topoisomerase Inhibitors class.
The emetic potential of this drug class is:
- All low except for topotecan (moderate)
Describe the extravasation risk and management strategies for the Topoisomerase Inhibitors class.
The extravasation risk and management strategies for this drug class are as follows:
- All irritants except for mitoxantrone (irritant with vesicant like properties)
Describe the metabolism of lrinotecan.
The metabolism of this drug is as follows:
- In patients with hepatic dysfunction, clearance is decreased and exposure to the active metabolite (SN-38) is increased proportional to the degree of hepatic impairment.
Describe the metabolism of Etoposide.
The metabolism of this drug is as follows:
- In renal function impairment, total body clearance is reduced, AUC is increased, and Vd is lower.
Describe the metabolism of Topotecan.
The metabolism of this drug is as follows:
- AUC after oral administration is 30% higher in Asian patients as compared to white patients.
What are the notable ADRs of lrinotecan?
The notable ADRs of this drug are:
- Diarrhea
- Neutropenia if homozygous for the UGT1A1*28 allele
What drug(s) of the Topoisomerase Inhibitors class is notable for causing Diarrhea?
The drugs in this class notable for cause this condition are:
- Irinotecan
Describe the strategy and rationale for management of EARLY onset diarrhea caused by Irinotecan.
The strategy and rationale for management of this condition caused by this drug are:
- Early-onset diarrhea occurs during or within 24 hours of infusion.
- This is caused by direct inhibition of acetylcholinesterase by the drug and is accompanied with cholinergic symptoms such as cramps, diaphoresis, flushing, salivation, visual disturbances, and lacrimation.
- Acute diarrhea is treated with atropine 0.25-1 mg SO or IV. Patients may also be given atropine as secondary prophylaxis after experiencing acute diarrhea in previous chemotherapy cycles.
Describe the strategy and rationale for management of LATE onset diarrhea caused by Irinotecan.
The strategy and rationale for management of this condition caused by this drug are:
- Late-onset diarrhea is the dose limiting toxicity of this drug and typically occurs >24 hours after drug administration (median time to onset is 6 days).
- This is thought to occur due to secretory processes caused by the active metabolite of the drug.
- Late onset diarrhea is treated with high dose loperamide and supportive care including fluids if needed.
- Patient should be instructed to take loperamide 4 mg at first sign of diarrhea, followed by 2 mg every 2 hours (4 mg every 4 hours at night) until 12 hours following last bowel movement up to 24 mg/day. Exceeding the daily limit of loperamide 16 mg/day is recommended for treatment of irinotecan-associated diarrhea in adults.
- Atropine has no role in the treatment of late onset diarrhea.
Describe the strategy and rationale for management of neutropenia caused by Irinotecan.
The strategy and rationale for management of this condition caused by this drug are:
- A test is available for genotyping of UGT1A1, however, use of the test is not widely accepted as dose reductions are already recommended in patients who have experienced toxicity regardless of genotype.
What are the risk factors for developing neutropenia with Irinotecan?
Risk factors for developing this ADR with this drug/class are:
- Homozygous for the UGT1A1*28 allele are at increased risk.
- Heterozygous carriers may also be at increased neutropenic risk, however, most patients have tolerated normal starting doses
What drugs are in the Vinca Alkaloids class?
Drugs in this class are:
- Vincristine
- Vinorelbine
- Vinblastine
What is the brand name of Vincristine?
The brand name of this generic drug is:
- Oncovin
What is the brand name of Vinorelbine?
The brand name of this generic drug is:
- Navelbine
What is the brand name of Vinblastine?
The brand name of this generic drug is:
- Velban
What is the generic of name of Oncovin?
The generic name of this brand name drug is:
- Vincristine
What is the generic of name of Navelbine?
The generic name of this brand name drug is:
- Vinorelbine
What is the generic of name of Velban?
The generic name of this brand name drug is:
- Vinblastine
What are the main indications for use of Vincristine?
The main indications of this drug are:
- Acute Lymphoblastic Leukemia
- Non-Hodgkin Lymphoma
- Rhabdomyosarcoma
- Central nervous system tumors
- Chronic lymphocytic leukemia/small lymphocytic leukemia
- Ewing sarcoma
- Hodgkin Lymphoma
What are the main indications for use of Vinorelbine?
The main indications of this drug are:
- Hodgkin Lymphoma
- Soft Tissue Sarcoma
- Non-small cell Lung cancer
- Small-cell Lung cancer
- Breast Cancer
- Cervical Cancer
- Ovarian cancer
- Mesothelioma
What are the main indications for use of Vinblastine?
The main indications of this drug are:
- Hodgkin Lymphoma
- Soft Tissue Sarcoma
- Testicular cancer
- Kaposi Sarcoma
- Bladder cancer
- Non-small cell Lung cancer
