High risk drugs Flashcards
• antibiotics • anticoagulants • antiHTN • chemotherapy • insulins • antidiabetic drugs • drugs with a narrow therapeutic index • non-steroidal anti-inflammatory drugs • methotrexate • opiates • parenteral drugs
Methotrexate adverse effects that patients should report which may indicate toxicity.
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
MTX MOA?
Indicated for?
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
MTX dosing info
Pt counselling
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.
MTX pulmonary toxicity
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.
Liver toxicity MTX
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.
Gastro-intestinal toxicity MTX
Manufacturuer advises withdraw treatment if stomatitis or diarrhoea develops—may be first sign of gastro-intestinal toxicity.
Blood count MTX
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.
Give folic acid to reduce side-effects.MTX
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.
Contraception MTX
Pregnancy
BF
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.
MTX monitoring
- before treatment
- during treatment
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.
Folinic acid helps
MTX
Folinic acid following MTX administration helps to prevent MTX-induced mucositis and myelosuppression.
T or F for MTX
Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.
True
T or F for MTX
NSAIDs can be used safely with MTX except for ibuprofen only
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.
Patient information for MTX
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
MTX interactions
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
Signs of renal tox
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
Signs liver toxicity
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.
Blood dyscrasias
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
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
Trimethoprim
MTX side effects
SE: skin reactions, diarrhoea, GI SE, anaemia, fatigue, increased risk of infection, ulcers
Which of the following have a cumulative dose of 100g? A. Streptomycin B. Trimethoprim C. Doxycycline D. Linezolid
Streptomycin
SE increase after cumulative dose
Which of the following is Ben Pen not given as?
- intravenously
- intramuscular
- intrathecal
- subcutaneously
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
Which of the following is drug of choice for PCP? A. Co-amoxiclav B. Co-fluampicil C. Co-trimoxazole D. Erythromycin
Co-trimoxazole
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
– Co-fluampicil; hepatic disorders
– Flucloxacillin; hepatic disorders
– Quinolones; convulsions (+NSAIDs), tendon damage
– Linezolid; optic neuropathy & blood disorders
– Itraconazole; heart failure
– Chloroquine; ocular toxicity
Treatment 1st line and 2nd line of:
- Bites
- CAP (changes w severity - low)
- C. Diff
- Cellulitis
- Impetigo
- Septicaemia
- Throat infections
- 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
Warfarin dose: 5 or 10mg OD for 2 days, then base on INR
A. Immediate anticoagulation
B: Atrial Fibrillation
C. Rapid anticoagulation
- 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
How long do oral anticoagulatns take for anticoagulant effect?
- warfarin sodium
- acenocoumarol
- phenindione
48-72 hrs
CI: 48-hrs post-partum, haemorrhagic stroke, significant bleeding
A. Warfarin
B. Lithium
C. Phenytoin
D. Carbamazepine
Warfarin
T or F
The risk of bleeding with aspirin and warfarin sodium dual therapy is lower than with clopidogrel and warfarin sodium
T
Indications for DOACs
apixaban, dabigatran, edoxaban and rivaroxaban
– 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.
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
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.
Warfarin target INR 2.5 and 3.5 are for what indications?
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
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
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
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?
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
Anticoagulants are of less use in preventing thrombus formation in arteries- why?
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.
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
2-3 days
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
https://bnf.nice.org.uk/treatment-summary/oral-anticoagulants.html
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
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.
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
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.
Strong inhibitors of CYP3A4 and P-glycoprotein increase apixaban levels and manufacturer advises to avoid these drugs
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
Switching from warfarin to apixaban:
Stop warfarin, and measure the international normalized ratio (INR)
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.
Switching from apixaban to warfarin
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).
