Pyrimidine Antagonist

Question 1

What drugs are in the Pyrimidine Antagonist class?

Answer 1

Drugs in this class are:
- Gemcitabine
- 5Fluorouracil (5FU)
- Capecitabine
- Cytarabine
- Floxuridine

Question 2

What is the brand name of Gemcitabine?

Answer 2

The brand name of this generic drug is:
- Infugem
- Gemzar

Question 3

What is the brand name of 5Fluorouracil?

Answer 3

The brand name of this generic drug is:
- Adrucil

Question 4

What is the brand name of Capecitabine?

Answer 4

The brand name of this generic drug is:
- Xeloda

Question 5

What is the brand name of Cytarabine?

Answer 5

The brand name of this generic drug is:
- AraC
- Cytosar

Question 6

What is the brand name of Floxuridine?

Answer 6

The brand name of this generic drug is:
- Fluorouridine deoxyribose

Question 7

What is the generic of name of Infugem?

Answer 7

The generic name of this brand name drug is:
- Gemcitabine

Question 8

What is the generic of name of Gemzar?

Answer 8

The generic name of this brand name drug is:
- Gemcitabine

Question 9

What is the generic of name of Adrucil?

Answer 9

The generic name of this brand name drug is:
- 5Fluorouracil

Question 10

What is the generic of name of Xeloda?

Answer 10

The generic name of this brand name drug is:
- Capecitabine

Question 11

What is the generic of name of AraC?

Answer 11

The generic name of this brand name drug is:
- Cytarabine

Question 12

What is the generic of name of Cytosar?

Answer 12

The generic name of this brand name drug is:
- Cytarabine

Question 13

What is the generic of name of Fluorouridine deoxyribose?

Answer 13

The generic name of this brand name drug is:
- Floxuridine

Question 14

What are the main indications for use of Gemcitabine?

Answer 14

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

Question 15

What are the main indications for use of 5Fluorouracil?

Answer 15

The main indications of this drug are:
- Anal Cancer
- Breast Cancer
- Colorectal Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancers
- Pancreatic Cancer

Question 16

What are the main indications for use of Capecitabine?

Answer 16

The main indications of this drug are:
- Anal Cancer
- Breast Cancer
- Colorectal Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancers
- Pancreatic Cancer

Question 17

What is the class and MOA of Gemcitabine?

Answer 17

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.

Question 18

What is the class and MOA of 5Fluorouracil?

Answer 18

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

Question 19

What is the class and MOA of Capecitabine?

Answer 19

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

Question 20

What is the class and MOA of Cytarabine?

Answer 20

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.

Question 21

What is the class and MOA of Floxuridine?

Answer 21

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.

Question 22

What are the notable monitoring parameters for 5Fluorouracil?

Answer 22

The notable monitoring parameters for this drug are:
- Monitor INR closely if patients are receiving concomitant warfarin therapy due to a drug-drug interaction.

Question 23

What are the notable monitoring parameters for Capecitabine?

Answer 23

The notable monitoring parameters for this drug are:
- Monitor INR closely if patients are receiving concomitant warfarin therapy due to a drug-drug interaction.

Question 24

What are the notable/common monitoring parameters for the Pyrimidine Antagonist class?

Answer 24

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.

Question 25

What drug(s) notably require monitoring of INR if on concomitant warfarin therapy?

Answer 25

Drug(s) notably requiring this monitoring are:
- 5Fluorouracil
- Capecitabine

Question 26

What is the emetic potential of 5Fluorouracil?

Answer 26

The emetic potential of this drug is:
- Low

Question 27

What is the emetic potential of Capecitabine?

Answer 27

The emetic potential of this drug is:
- Low

Question 28

What is the emetic potential of Gemcitabine?

Answer 28

The emetic potential of this drug is:
- Low

Question 29

What is the emetic potential of Cytarabine?

Answer 29

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.

Question 30

Describe the emetic potential of the Pyrimidine Antagonist class.

Answer 30

The emetic potential of this drug class is:
- Low (except for Cytarabine*)

Question 31

Describe the extravasation risk and management strategies for the Pyrimidine Antagonist class.

Answer 31

The extravasation risk and management strategies for this drug class are as follows:
- Fluorouracil may be an irritant. avoid extravasation.

Question 32

Describe the administration of 5Fluorouracil.

Answer 32

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.

Question 33

Describe the administration of Capecitabine.

Answer 33

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.

Question 34

Describe the administration of Floxuridine.

Answer 34

The administration of this drug is described as follows:
- Administered as a continuous hepatic intra-arterial infusion using an infusion pump.

Question 35

Describe the metabolism of 5Fluorouracil.

Answer 35

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)

Question 36

Describe the metabolism of Capecitabine.

Answer 36

The metabolism of this drug is as follows:
- Enzymatically metabolized to fluorouracil.

Question 37

Describe the metabolism of Gemcitabine.

Answer 37

The metabolism of this drug is as follows:
- Metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside metabolites

Question 38

Describe the metabolism of Cytarabine.

Answer 38

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.

Question 39

What are the notable ADRs of 5Fluorouracil?

Answer 39

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.

Question 40

What are the notable ADRs of Capecitabine?

Answer 40

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.

Question 41

What are the notable ADRs of Cytarabine?

Answer 41

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.

Question 42

What are the notable/common ADRs of the Pyrimidine Antagonist class?

Answer 42

The notable/common ADRs of this drug class are:
- Hand/Foot Syndrome (especially 5Fluorouracil and Capecitabine)

Question 43

What drug(s) of the Pyrimidine Antagonist class is notable for causing Hand/Foot Syndrome?

Answer 43

The drugs in this class notable for cause this condition are:
- 5Fluorouracil and Capecitabine (and to a lesser degree Cytarabine)

Question 44

Describe the strategy and rationale for management of intolerability to 5Fluorouracil.

Answer 44

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)

Question 45

Describe the strategy and rationale for management of Hand/Foot Syndrome caused by 5Fluorouracil/Capecitabine.

Answer 45

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.

Question 46

Describe the strategy and rationale for management of Cytarabine Syndrome.

Answer 46

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

Question 47

What are the clinical pearls of Capecitabine?

Answer 47

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)