High risk drugs

Question 1

Methotrexate adverse effects that patients should report which may indicate toxicity.

Answer 1

INFECTION / BLOOD DYSCRASIAS: sore throat, bruising or mouth ulcers
LIVER IMPAIRMENT: nausea, vomiting or dark urine
PULMONARY: dyspnoea or cough
BONE MARROW SUPPRESSION: ^drop WBC/platelet=> withdrawal, thrombocytopenia, liver cirrhosis

Question 2

MTX MOA?

Indicated for?

Answer 2

inhibit dihydrofolate reductase (DHFR), the enzyme responsible for the reduction of folic acid to its active form, which is an essential cofactor for purine and thymidylic acid synthesis, and hence DNA production

Chemotherapy; BC, neoplastic diseases
Autoimmune conditions: Crohns (unlicensed), RA, Psoriasis

Question 3

MTX dosing info

Pt counselling

Answer 3

Usually once weekly
Comes as 2.5mg and 10mg tabs
Can be taken with or without food
Drink enough fluid, dehydration increases toxicity risk
Do not take extra doses for symptom relief. Relief of symptoms is gradual, begins in 3-6 weeks after starting. Continued improvement occurs during the first 12 weeks of taking the medicine.

Question 4

MTX pulmonary toxicity

Answer 4

Pulmonary toxicity may be a special problem in rheumatoid arthritis. Manufacturer advises patients to seek medical attention if dyspnoea, cough or fever develops; monitor for symptoms at each visit—discontinue if pneumonitis suspected.

Question 5

Liver toxicity MTX

Answer 5

Tx should not be started or discontinued if any abnormality of LFT / biopsy is present.
Abnormalities can return to normal in 2 weeks after which tx may be recommenced. Persistent increases in liver transaminases may warrant dose reduction / discontinuation.

Question 6

Gastro-intestinal toxicity MTX

Answer 6

Manufacturuer advises withdraw treatment if stomatitis or diarrhoea develops—may be first sign of gastro-intestinal toxicity.

Question 7

Blood count MTX

Answer 7

Bone marrow suppression can occur abruptly; factors likely to increase toxicity: advanced age, renal impairment, and concomitant use with another anti-folate drug (e.g. trimethoprim). Manufacturer advises a clinically significant drop in white cell count or platelet count calls for immediate withdrawal of methotrexate and introduction of supportive therapy.

Question 8

Give folic acid to reduce side-effects.MTX

Answer 8

Folic acid decreases mucosal and gastrointestinal SE of MTX and may prevent hepatotoxicity; no evidence of a reduction in haematological SE. Folinic acid (as calcium folinate) may be required in acute toxicity.

Question 9

Contraception MTX
Pregnancy
BF

Answer 9

Manufacturer advises effective contraception during and for at least 6 months after treatment in men and women.
Avoid (teratogenic; fertility may be reduced during therapy but this may be reversible).
Discontinue breast-feeding—present in milk.

Question 10

MTX monitoring

• before treatment
• during treatment

Answer 10

Before tx: FBC RFT LFT

low-dose methotrexate patients should:

• have FBC, RFT, LFT repeated every 1–2 weeks until therapy stabilised, thereafter pts should be monitored every 2–3 months.
• report all symptoms + signs suggestive of infection, especially sore throat

Treatment with folinic acid (as calcium folinate) may be required in acute toxicity.

Question 11

Folinic acid helps

MTX

Answer 11

Folinic acid following MTX administration helps to prevent MTX-induced mucositis and myelosuppression.

Question 12

T or F for MTX

Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.

Answer 12

True

Question 13

T or F for MTX

NSAIDs can be used safely with MTX except for ibuprofen only

Answer 13

False

Patients should be counselled on the dose, treatment booklet, and the use of NSAIDs. There is some effect it can have as prostaglandin inhibition in kidneys may reduce renal perfusion affecting MTX clearance.

Question 14

Patient information for MTX

Answer 14

Patients and their carers should be warned to report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising, and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort and dark urine), and respiratory effects (e.g. shortness of breath).
Methotrexate treatment booklets
A patient alert card should be provided to patients on once-weekly dosing
Avoid alcohol
Sunscreen for sun sensitivity
Folic acid on different day to MTX
Try to avoid taking with milk rich foods / caffeine
Avoid touching tab with hands

Question 15

MTX interactions

Answer 15

PPI, ^MTX, reduce prostaglandin reduced renal perfusion and MTX clearance
Trimethoprim, ^MTX nephrotoxicity, both folate antagonists
Vaccines ^risk of infection
Echinaecea, caffeine
NSAIDs
Penicillins ^MTX, as weak acids can compete @kidney

Question 16

Signs of renal tox

Answer 16

Lethargy / Weakness (anaemia)
SOB
Generalized swelling (edema)
Loss of appetite
Congestive heart failure
Metabolic acidosis
High blood potassium(hyperkalemia)
Fatal heart rhythm disturbances (arrhythmias) including ventricular tachycardia and ventricularfibrillation

Question 17

Signs liver toxicity

Answer 17

Skin and eyes that appear yellowish (jaundice)
Abdominal pain and swelling.
Swelling in the legs and ankles.
Itchy skin.
Dark urine color.
Pale stool color.
Chronic fatigue.
Nausea or vomiting.

Question 18

Blood dyscrasias

Answer 18

medical conditions (hematologic disorders) that may affect the cellular or plasma components of theblood, the bone marrow, or the lymph tissue

Signs: sore throat, bruising, mouth ulcers

Question 19

Mr Smith is 75 yo suffers from RA.
Taking MTX for the past 3 months.
GP prescribed him an antibiotic for infection.
Mr Smith brings the prescription to your pharmacy, he tells you he was told by his grandson that certain antibiotics may interact with methotrexate. Which antibiotic below must be avoided when on MTX?

A. Amoxicillin
B. Trimethoprim
C. Flucloxacillin
D. Erythromycin
E. Nitrofurantoin

Answer 19

Trimethoprim

Question 20

MTX side effects

Answer 20

SE: skin reactions, diarrhoea, GI SE, anaemia, fatigue, increased risk of infection, ulcers

Question 21

Which of the following have a cumulative dose of 100g?
A. Streptomycin
B. Trimethoprim
C. Doxycycline
D. Linezolid

Answer 21

Streptomycin

SE increase after cumulative dose

Question 22

Which of the following is Ben Pen not given as?

• intravenously
• intramuscular
• intrathecal
• subcutaneously

Answer 22

Oral penicillin G is no longer used because it is subject to degradation in the presence of stomach acid.

Benpen is also not recommended to be given intrathecally due to safety

Question 23

Which of the following is drug of choice for PCP?
A. Co-amoxiclav
B. Co-fluampicil
C. Co-trimoxazole
D. Erythromycin

Answer 23

Co-trimoxazole

Question 24

MAtch important safety info to the antibiotic
hepatic disorders - convulsions and tendon damage - heart failure - ocular toxicity - optic neuropathy and blood disorders

A. Co-fluampicil
B. Linezolid
C. Quinolones
D. Flucloxacillin
E. Chloroquine
F. Itraconazole

Answer 24

– Co-fluampicil; hepatic disorders
– Flucloxacillin; hepatic disorders
– Quinolones; convulsions (+NSAIDs), tendon damage
– Linezolid; optic neuropathy & blood disorders
– Itraconazole; heart failure
– Chloroquine; ocular toxicity

Question 25

Treatment 1st line and 2nd line of:

• Bites
• CAP (changes w severity - low)
• C. Diff
• Cellulitis
• Impetigo
• Septicaemia
• Throat infections

Answer 25

• Bites = 1st: Co-amox = 2nd: Doxy + Metronidazole
• CAP (changes w severity– low)
  1st: Amoxicillin = 2nd: Doxy / Clarithromycin
• C. Diff = 1st: Metronidazole = 2nd: PO Vancomycin
• Cellulitis = 1st: Flucloxacillin = 2nd: Cinda or clarithromycin
• Impetigo (wide spread) = 1st Fluclox. = 2nd: Clarithromycin
• Meningitis in community = 1st: Benzylpenicillin
  2nd: Cefotaxime, Chloramphenicol
• Septicaemia (inc. neut sepsis)
  1st: Tazocin = 2nd: Cefuroxime, Meropenem
• Throat infections = 1st: Phenoxymethylpenicillin
  2nd: Clarithromycin

Question 26

Warfarin dose: 5 or 10mg OD for 2 days, then base on INR
A. Immediate anticoagulation
B: Atrial Fibrillation
C. Rapid anticoagulation

Answer 26

- Rapid anticoag 
5 or 10mg OD for 2 days, then base on INR
- AF 
Achieve anticoag in 3-4wks
1 or 2mg OD, then base on INR
- Immediate effect 
Use heparin/LMWH

Question 27

How long do oral anticoagulatns take for anticoagulant effect?

• warfarin sodium
• acenocoumarol
• phenindione

Answer 27

48-72 hrs

Question 28

CI: 48-hrs post-partum, haemorrhagic stroke, significant bleeding

A. Warfarin
B. Lithium
C. Phenytoin
D. Carbamazepine

Answer 28

Warfarin

Question 29

T or F

The risk of bleeding with aspirin and warfarin sodium dual therapy is lower than with clopidogrel and warfarin sodium

Answer 29

T

Question 30

Indications for DOACs

apixaban, dabigatran, edoxaban and rivaroxaban

Answer 30

– Instead of warfarin for non-valvular atrial fibrillation (NVAF)
– preventing stroke and systemic embolism
– treatment of PE and DVT
– prevention of recurrent DVT and PE in adults after diagnosis of acute DVT.

apixaban, dabigatran, and rivaroxaban
– VTE prophylaxis in adults after elective hip or knee replacement surgery.

Question 31

Prophylaxis of atherothrombotic events (with aspirin alone, or with aspirin and clopidogrel, or ticlodipine) after an acute coronary syndrome in people with elevated cardiac biomarkers.

Apixaban
Dabigatran
Rivaroxaban
Edoxaban
Warfarin
LMWH

Answer 31

Rivaroxaban:
– prophylaxis of atherothrombotic events (with aspirin alone, or with aspirin and clopidogrel, or ticlodipine) after an acute coronary syndrome in people with
elevated cardiac biomarkers.

Question 32

Warfarin target INR 2.5 and 3.5 are for what indications?

Answer 32

INR:
– 2.5; Tx of DVT, PE, AF, cardioversion, dilated cardiomyopathy, mitral stenosis, heart valves (but may vary), arterial embolism (embolectomy), MI
– 3.5; recurrent DVT or PE

Question 33

For these indications how long are patients on Warfarin for?
Isolated calf-vein DVT 
Provoked VTE 
Unprovoked DVT or PE 
Recurrent DVT/PE
AF
Heart Valve

Answer 33

Indication Duration
Isolated calf-vein DVT = 6 wks
Provoked VTE = 3 months
Unprovoked DVT or PE = At least 3 months (6 months to long-term possibly)

LONG TERM: Recurrent DVT/PE, AF, Heart Valve

Question 34

Warfarin stopping for surgery peri-operative recommendations

• When should warfarin be stopped prior to surgery?
• What should be given if INR≥1.5 day before surgery?
• When can warfarin be resumed?
• Patients stopping warfarin prior to surgery who are considered to be at high risk of thromboembolism (e.g. those with a venous thromboembolic event within the last 3 months, AF with previous stroke or transient ischaemic attack, or mitral mechanical heart valve) may require interim therapy of what?
• What would happen if there is surgical emergency?

Answer 34

Surgery:
– Stop 5 days before elective
– (unlicensed IV=> PO) Give Phytomenadione day before if INR≥1.5
_ If haemostasis adequate, warfarin resumed on evening of surgery or next day.
– Bridging LMWH if high risk (eg VTE last 3m) but stop LMWH at least 24 hrs before surgery; if the surgery carries a high risk of bleeding, LMWH should not be restarted until at least 48 hours after surgery.
– Emergency – surgery delay 6-12hrs + IV phytomenadione
– Emergency – no delay prothrombin + phytomenadione IV

Question 35

Anticoagulants are of less use in preventing thrombus formation in arteries- why?

Answer 35

Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster-flowing vessels thrombi are composed mainly of platelets with little fibrin.

Question 36

if the anticoagulant is stopped but not reversed, the INR should be measured \_\_\_\_\_\_\_\_\_\_ later to ensure that it is falling
A. one day
B. 2-3 days
C. one week
D. one month
E. 10 days

Answer 36

2-3 days

Question 37

Warfarin outcomes and recommendations:

• major bleeding
• INR >8 with minor bleeding
• INR >8 no bleeding
• INR 5 - 8 minor bleeding
• INR 5 - 8 no bleeding
• unexpected bleeding at therapeutic levels

Answer 37

https://bnf.nice.org.uk/treatment-summary/oral-anticoagulants.html

Question 38

Apixaban dose for:
Prophylaxis of stroke and systemic embolism in NVAF
DVT and PE
Prevention of recurrent DVT & PE (following Tx dosing)
Prevention VTE for hip replacement
Prevention VTE for knee replacement

Answer 38

Prophylaxis of stroke and systemic embolism in NVAF
- 5mg OD long term
Tx for DVT and PE
- 10mg BD for 7 days followed by 5mg BD min duration of 3 months and further dependent on risk factors
Prevention of DVT and PE
- 2.5mg BD duration assessment benefit:risk
Prevention VTE for hip replacement
- 2.5 mg BD for 32–38 days, started 12–24 hrs after surgery. Knee replacement: duration 10 - 14 days.

Question 39

Normal apixaban dose is 5mg but in what situations would it be 2.5mg?
Indication: Prophylaxis of stroke and systemic embolism in adults with non-valvular AF and at least one risk factor, such as previous stroke or transient ischaemic attack, symptomatic HF, DB, HTN, or age 75 years and over

Answer 39

At least two of the following characteristics:
1. age 80 years or over, body weight 60 kg or less, serum creatinine 133 micromol/L or over.
2. Creatinine clearance (CrCl) 15–29 mL/minute.
Treatment is usually long term.

Question 40

Strong inhibitors of CYP3A4 and P-glycoprotein increase apixaban levels and manufacturer advises to avoid these drugs

Answer 40

AVOID: itraconazole, ketoconazole, and HIV protease inhibitors (e.g. ritonavir) — ^[apixaban]

Strong inhibitors of both CYP3A4 and P-gp, such as amiodarone, clarithromycin, diltiazem, fluconazole, quinidine, and verapamil, [apixaban] increased to a lesser extent. No dose adjustment for apixaban is required with these drugs, but the person should be monitored for signs of bleeding or anaemia

Question 41

Switching from warfarin to apixaban:

Stop warfarin, and measure the international normalized ratio (INR)

Answer 41

If the INR < 2, start apixaban.
If the INR 2 - 2.5, start apixaban the next day.
If the INR > 2.5, wait until the person’s INR has dropped to less than 2 before starting apixaban.

Question 42

Switching from apixaban to warfarin

Answer 42

Start warfarin, but do not stop apixaban.

After at least 2 days of concurrent tx: measure INR prior to the next dose of apixaban.
- INR in target range: stop apixaban and continue with warfarin.
- INR is not in range, continue warfarin and apixaban concurrently until the person’s INR is in the target range, then stop apixaban. Warfarin has a slow onset of action and it may take 5–10 days before the INR is within range.
After treatment with apixaban has stopped:
- Measure the INR after 24 hours to ensure adequate anticoagulation.
- Monitor the person’s INR closely (e.g. once a week) in the first month of warfarin treatment until the person has three consecutive stable INR values (for example between 2–3).