eScript 2 Flashcards
What medication can increase the risk of ADR of rhabdomyolysis?
Simvastatin. Statin related myotoxicity is dose-related and range from mild aching to rhabdomyolysis. Age, female, genetic predisposition and renal impairment also increase risk. Diltiazem inhibits breakdown of simvastatin so increases serum conc.
Therefore, max recommended dose of simvastatin with diltiazem with amlodipine is 20mg per day.
Acute management of rhabdomyolysis?
Stop precipitating drugs. If renal failure is established, urgent dialysis. If not, IV fluids to prevent renal failure. Give sodium bicarb to alkalinize the urine and reduce the precipitation of myoglobin in the renal tubules. Monitor potassium.
What are Type A ADRs?
Type A= augmented. They’re generally dose-related, common, predictable, related to the pharmacology, unlikely to be fatal.
E.g. digoxin toxicity or constipation with opioid analgesics, bruising with warfarin
What are Type B ADRs?
Type B= bizarre. Not dose-related, uncommon, unpredictable, not related to the pharmacology, often fatal.
E.g. penicillin hypersensitivity, malignant hyperthermia, hepatitis caused by anaesthetic agents.
Type C
Chronic. E.g. long term steroids leading to suppression of the hypothalamic-pituitary- adrenal axis.
Type D
Delayed. Becomes apparent some time after use of the drug. E.g. carcinogenesis
Type E
End of treatment. Occurs soon after withdrawal of the drug e.g. opiate withdrawal syndrome
Type F
Failure. Common, dose-related, often due to interactions. E.g. Failure of the OCP in the presence of an enzyme inducer.
What is the DOTS classification for ADRs?
ADRs are dependent on Dose, Timing and Susceptibility.
Dose- hypersusceptibility reaction (occurs at much lower doses than therapeutic), Collateral effects (occurs at therapeutic doses), Toxic effects (occurs at doses higher than therap
eutic)
Time- time dependent or independent
Susceptibilities- Immunological reaction e.g. allergies, genetics e.g. G6PD deficiency, age (older adults and children) , sex (women have more ADRs with mefloquine, drug-induced torsades de pointes, hyponatraemia with diuretics) ,physiology e.g. pregnancy, exogenous e.g. other drugs the patient may already be taking, disease states affecting the patient e.g. renal dysfunction, liver disease, CCF, DM, COPD etc
What is red man syndrome?
Occurs when vancomycin is administered too quickly
Is a withdrawal reaction an ADR?
Yes
What monitoring needs to be done with clozapine?
WCC, platelets and neutrophils for the risk of agranulocytosis
What monitoring is needed for methotrexate?
FBC, renal and LFTs at baseline, weekly until therapy stabilised and then every 2-3 months thereafter. To reduce risk of blood dyscrasias.
How often should lithium levels be taken?
Every 3 months
What is the yellow card scheme?
Collects spontaneous reports of suspected ADRs
ADRs that are very common occur in what percentage of patients?
More than 10%
ADRs that are common occur in what % of patients?
More than 1% and less than 10%
Which medicine should be avoided in a patient with G6PD deficiency?
Ciprofloxacin
Quinolones such as ciprofloxacin should be avoided in G6PD-deficient individuals, as should aspirin.
However, low dose aspirin can be used.
How do miconazole (anti-fungal) and warfarin interact?
Miconazole inhibits the cytochrome P450 enzyme CYP2C9, of which warfarin is a substrate. This causes an increase in the drug concentration, increasing INR.
What drug interaction are women more susceptible to?
Women tend to eliminate drugs quicker. However women are more prone to serious drug side-effect torsades de pointes.
Factors that increase risk of drug interactions?
Older age or neonate, gender, comorbidities e.g. renal failure, smoking, alcohol or illicit drug use,
What are the two classifications of drug interactions?
Pharmacodynamic and pharmacokinetic
What are pharmacodynamic drug interactions?
Drugs amplify or negate each other’s pharmacological effects. E.g. the interaction between sildenafil and GTN. Both drugs increase cyclic GMP which can cause severe hypotension or even an MI.
Diet advice for people on warfarin?
Not to drastically change their diet with regard to green leafy veg and other food containing vit K
Give an example of a drug-food reaction with ACE inhibitors?
Avoid potassium containing salt-> increases risk of hyperkalaemia with ACEi or potassium-sparing diuretics
What is a pharmacokinetic interaction?
When one drug, dietary or herbal chemical impacts on the biotransformation (metabolism) of a drug, or even their distribution within the body.
What is the drug interaction between rifampicin and COCP?
Pharmacokinetic interactioin. Rifampicin induces drug metabolising enzymes in the liver, inducing P450 enzyme activity. This can reduce the effectiveness of oestrogens and progestogens.
What is the drug interaction between verapamil and beta blockers?
Pharmacodynamic interaction. They have similar pharmacological effects, being negatively inotropic. This can cause marked bradycardia, hypotension and even asystole. This risk also extends to oral verapamil with topical timolol eye drops.
What is the drug interaction between warfarin and some macrolide antibacterials such as erythromycin and clarithromycin?
Pharmacokinetic. They interact with warfarin to increase INR, as they inhibit CYP3A4 which metabolises some warfarin.
How do aminoglycosides and loop diuretics interact?
Pharmacodynamic. They can both cause ototoxicity.
How do lithium salts and ramipril interact?
Pharmacokinetic. Reduced excretion of lithium salts can cause toxicity. Symptoms inc N&V&D, neuromuscular symptoms such as tremors, dystonia, hyperreflexia and ataxia. ACE inhibitors reduce GFR and increase sodium loss, which is linked to their promotion of lithium retention.
What is the interaction between warfarin and NSAIDs?
Pharmacodynamic. Increased risk of bleeding. NSAIDs inhibit COX, which is responsible for the production of gastro-protective prostaglandins.
What is the problem with women who need emergency contraception who have taken carbamazepine within the last 4 weeks?
They should ideally use a non-hormonal emergency contraceptive e.g. IUD. If not, double the dose of levonorgestrel from 1.5mg to 3mg
What are influx and efflux pumps?
Influx increases absorption into cells (OATPs) while efflux prevent over absorption into cells (P-glycoprotein). Some tumours can produce P-glycoprotein, causing resistance to medications, where rifampicin can inhibit OATPs causing atorvastatin to be saved from biotransformation as it will not enter liver cells and go direct into the systemic conc. This increases plasma conc.
Fexofenadine absorption is effectively prevented by grapefruit juice, which contains inhibitors of the OATPs.
What process can reduce drug absorption and how can this be prevented?
First pass metabolism.
Can be avoided by giving a drug IV.
What are the most powerful inducers of CYPS?
Rifampicin
St John’s Wort
First generation anticonvulsants e.g. phenytoin, carbamazepine, phenobarbitol
Name some CYP inhibitors?
Reversible- azole antifungals such as fluconazole
Irreversible- erythromycin
Non-drug inhibitors e.g. grapefruit, cranberry juice
Effects of the following herbal interactions: Garlic, Ginseng, Glucosamine, St John’s Wort, Liquorice?
Garlic inhibits platelet aggregation= increased bleeding risk
Ginseng can cause hypoglycaemia
Glucosamine can interact with warfarin and increase INR
St John’s Wort interacts with antidepressants. Can increase risk of serotonin syndrome or hypertensive crisis when prescribed with MAOIs. It also induces the metabolism of warfarin causing a reduced INR. Also reduced conc of oestrogen and progesterone reducing contraceptive cover.
Liquorice can cause hypokalaemia and therefore increase risk of digoxin toxicity if taken concomitantly.
how does methotrexate work and what can be used to reduce its toxicity?
Folic acid antagonist
Can use folinic acid “rescue” treatment
Oral iron reduces the absorption of which drug?
Ciprofloxacin
what is the definition of a mistake?
An error in formulating a plan of action
They can be classified as either knowledge-based (lack of) or rule-based (misapplication of a set of a rules to a new situation)
what is a slip error?
Occurs when one or more step is executed incorrectly
Action-based error
what is a lapse?
Occurs when one or more step is omitted
Memory-based error
What is the effect of erythromycin on warfarin?
Erythromycin enhances the anticoagulation effect of warfarin which can result in increased INR and increases risk of bleeding
Interaction between ciprofloxacin and ferrous sulphate?
Ferrous sulphate reduces absorption of ciprofloxacin
can diclofenac be continued post stroke?
It is contraindicated post stroke. Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high dose (150 mg daily) and in long-term treatment may be associated with a small increased risk of serious arterial thrombotic events (for example myocardial infarction or stroke)
what is bioavailability?
Bioavailability is the proportion of the medicine that finally makes the systemic circulation, where it is available to act at the ‘effector site’.
what are the basic prescription requirements for a controlled drug?
Name and address of the patient Age or date of birth if under 12 Signed by the prescriber Dated (prescriptions for Schedule 2,3 and 4 CDs are only valid for twenty-eight days) Be written so as to be indelible Contain a perscriber identifier
what are the additional prescription requirements for a controlled drug?
Dose
- For example, ‘as directed’ is not acceptable, but ‘One as directed’ or ‘One as required’ are legal.
Form of the preparation (e.g. tablets, capsules, oral liquid), even if only one form is available.
Strength, unless there is only one strength available.
Total quantity of the preparation or the number of dosage units in both words and figures.
what is an example of ‘the total quantity of the preparation or the number of dosage units to be in both words and figures’?
Morphine Sulfate MR capsules 10mg BD Supply 14 (fourteen) capsules
Morphine Sulfate Concentrated Oral Solution 100 mg/5 ml 1ml four times a day when required for breakthrough pain Supply 30 (thirty) mls
what is an unlicensed drug?
Unlicensed products do not have a UK marketing authorisation.
what is meant by off-label prescribing?
Off-label prescribing refers to the use of a drug that does have a marketing authorisation, but where its use is outside the terms of its licence. This may be at a different dose, indication, or patient group outlined in the ‘Summary of Product Characteristics’ (SPC).
what can happen if levothyroxine is started at a high dose after a period of cessation?
cardiac output is suddenly increased, and this can precipitate angina, palpitation, shortness of breath and even heart failure.
what can happen if clozapine is started at a high dose after over 48 hours cessation?
Increases the risk of orthostatic hypotension, which may be accompanied by cardiac or respiratory arrest.
what herbal medications can inhibit platelet aggregation?
Garlic, feverfew, Echinacea and ginseng
what herbal med can reduce the conc of lansoprazole?
St John’s Wort
what dilutent does amiodarone need to be given in?
5% glucose
after a dose change of levothyroxine, when should you monitor TFTs?
After a dose adjustment, you should wait 6-8 weeks before checking TFTs again.
How often should patients be monitored when on a maintenance dose of levothyroxine?
annually, provided their clinical status remains unchanged.
what monitoring does amiodarone need?
To avoid the risk of thyroid disorders, TFTs should be monitored before treatment with amiodarone is initiated, and every 6 months thereafter. Amiodarone is associated with both drug-induced hyperthyroidism and hypothyroidism
what monitoring does COCP need?
Blood pressure should be monitored every 6 months in women taking the combined oral contraceptive. In 1% of COC users, severe hypertension may be induced.
what monitoring does digoxin need?
Heart rate is monitored in hospital before the administration of digoxin, especially early in therapy. Heart rate is an indication of the pharmacodynamic effect of digoxin. Although plasma-digoxin concentration monitoring is available, its use tends to be reserved for the diagnosis of toxicity.
what monitoring does gentamicin need?
It has a narrow therapeutic window, and therefore the plasma concentration should be closely monitored. Monitoring requirements vary depending on whether the patient is receiving a once daily or multiple daily dose regimen
what monitoring does methotrexate need?
FBC should be closely monitored before, during and after treatment with methotrexate. FBCs are recommended every two weeks for two months, monthly for four months and then three monthly thereafter. If a clinically significant drop in white cell or platelet count develops, methotrexate should be withdrawn immediately. Patients should be advised to report all symptoms or signs suggestive of infection.
how is vitamin D status best assessed?
plasma 25-hydroxyvitamin D (i.e. 25(OH)D).
< 25 nmol/litre is deficient.
25-50 nmol/litre is deficient for some of the population e.g. low sunlight exposure, symptoms that are suggestive of vitamin D deficiency, documented osteoporosis or high fracture risk, treatment with antiresportive medicines for bone disease, raised PTH, taking antiepileptics or oral corticosteroids.
what should be monitored 1 month after treating with vitamin D?
The patient’s adjusted plasma calcium concentration should be checked one month after completing a loading regimen or commencing lower dose vitamin D supplementation. This is recommended as vitamin D treatment (particularly when combined with calcium supplementation) may unmask undiagnosed primary hyperparathyroidism
symptoms and signs of vit D toxicity?
hypercalcaemia- confusion, dehydration, muscle weakness, vomiting, and loss of appetite.
when should serum lithium conc be taken?
12 hours post dose
Symptoms of hypokalaemia?
<3.5
can be asymptomatic, or some people suffer from muscle weakness and cramps, fatigue, constipation, and palpitations
causes of hypokalaemia?
1) Drug causes- Excessive use of laxatives
Glucocorticoid therapy (e.g. prednisolone)
Insulin
Loop diuretics (e.g. furosemide)
Salbutamol
Some antibacterials (e.g. gentamicin, amphotericin)
Thiazide diuretics (e.g. bendroflumethiazide)
Theophylline
2) GI losses
3) Metabolic alkalosis- Low magnesium concentration
4) Mineralocorticoid excess (e.g. Cushing’s disease)
5) Excessive alcohol consumption
6) Renal Tubular acidosis
how can potassium be supplemented?
orally or IV potassium chloride in 0.9% saline
peripherally until exceeds conc 40mmol/L then centrally
what is hyperkalaemia classified as?
> 5.3
signs and symptoms of hyperkalaemia?
Nausea Muscle weakness ECG changes Ventricular fibrillation Cardiac arrest
causes of hyperkalaemia?
1) Drug causes-
ACE inhibitors
Acute digoxin overdose
Angiotensin-II receptor blockers
Heparin and low molecular weight heparins
NSAIDs
Penicillins
Potassium sparing diuretics (e.g. spironolactone)
Potassium supplementation (oral/intravenous)
Excessive dietary intake (e.g. Lo-salt)
2) Metabolic acidosis
3) Renal failure
4) Rhabdomyolysis/burns/trauma
how is calcium gluconate administered?
10 ml of calcium gluconate 10% solution, by slow intravenous injection over 3-5 minutes
how is calcium gluconate administered if the patient is on digoxin therapy?
The 10 ml of calcium gluconate 10% solution should be mixed with 100ml of glucose 5% and administered slowly over 20 minutes.
what is given to reduce the serum potassium concentration in hyperkalaemia?
Withdraw potassium supplements and any drugs that cause an increase in serum-potassium concentration.
Intravenous injection of 5-10 units soluble insulin (Actrapid®) with 50 ml glucose 50%, given over 5-15 minutes. This drives potassium into cells and therefore reduces the serum-potassium concentration
Salbutamol nebs
what is given to rid the body of excess potassium?
Calcium resonium- is an ion-exchange resin, which binds potassium and promotes its elimination from the body. It is given orally at a dose of 15 g three to four times a day (short-term only).
If potassium concentrations remain high or ECG changes persist despite treatment, dialysis may be necessary.
what is the most common formulation of insulin?
100units/ml
devices for administration of insulin?
Reusable pens and penfills Disposable pens Vial InnoLet Insulin pump
when prescribing and administering insulin, what info do you want?
The name of the insulin (as the brand name).
Usual dose (or dose range) of insulin.
The device used by the patient or their relative/carer to administer the insulin.
The ‘usual’ time of administration.
Whether they have an insulin passport or carbohydrate diary
what should you aim BG conc before and after meals?
Before meals: between 4 and 7 mmol/litre.
After meals: less than 9 mmol/litre.
what type of drug is gentamicin?
aminoglycoside
what can gentamicin be prescribed for?
Bacterial endocarditis
Surgical prophylaxis
Neutropenic sepsis
what condition is a contraindication for gentamicin?
myasthenia gravis
when should gentamicin levels be measured?
With ‘once daily dose regimens’, serum-gentamicin concentration should be measured before a second dose is administered to avoid toxicity.
6-14 hours after the first infusion when it is the trough (target conc less than 1 mg/litre)
what is the effect of renal dysfunction of gentamicin?
Any impairment in renal function can cause reduced elimination of gentamicin from the body and high serum-gentamicin concentrations as a result.
A high concentration can result in nephrotoxicity, which can further reduce the elimination of gentamicin. This can cause further nephrotoxicity and ototoxicity.
when can multiple daily dose regimens be used in gentamicin?
Ascites Children (practice may vary) Cystic fibrosis Endocarditis Extensive burns (of more than 20% of the total BSA) Pregnancy
what should once daily doses of gentamicin be calculated on?
actual body weight (ABW), unless the patient’s weight is 20% heavier than ideal body weight (IBW) or has a BMI of more than 30 kg/m2, in which case IBW should be used
what monitoring is needed for gentamicin?
Monitor renal function before and during treatment.
Monitor serum gentamicin concentration
when are peak and trough doses measured of gentamicin?
Peak: one hour post-dose (document the exact time)
Trough: measure pre-dose (document the exact time)
symptoms of gentamicin toxicity?
Tinnitus/deafness/balance problems Nausea and vomiting Renal dysfunction Colitis Stomatitis Blood dyscrasias (e.g. neutropenia).
what is vancomycin prescribed for?
IV- Septicaemia Febrile neutropenia Prophylaxis/treatment of endocarditis Orally- Treatment of Clostridium difficile - associated diarrhoea.
When should you measure the first serum-vancomycin concentration?
The trough concentration should be monitored in patients prescribed vancomycin.
This should take place before the 3rd to 6th dose.
36-72 hours
Monitoring not needed for oral doses
how is vancomycin normally prescribed?
Vancomycin has a half-life of approximately 5-7 hours. When administered as an intravenous infusion it is usually prescribed twice daily.
usually 1 g every 12 hours.
what is the dose adjustment for vacomycin?
Dose adjustment is necessary in renal dysfunction. This must be based on the patient’s creatinine clearance, and not their eGFR.
how is vancomycin administered?
loading dose then maintenance dose
Infuse over at least 60 minutes
what are the dangers of rapid infusion of vancomycin?
Rapid infusion can cause severe reactions such as cardiac arrest, cardiogenic shock and “red man syndrome”. Red man syndrome results from histamine release and usually occurs within a few minutes of starting the first infusion
signs of vancomycin toxicity?
Blood dyscrasias
Fever and chills
Nausea and vomiting
‘Red man’ syndrome: this is more likely to occur if the infusion is administered too quickly
Renal dysfunction
Skin disorders (including the potentially life threatening Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome)
mechanism of action of warfarin?
vitamin K antagonist
what is the effect of macrolide antimicrobials e.g. erythromycin on warfarin?
Increased monitoring is recommended when a patient is started on a macrolide antimicrobial. The INR should be monitored within three days of starting the course.
A target INR of 2.5 is recommended for most patients with atrial fibrillation. If the INR is increased with the concomitant prescribing of erythromycin, the dose of warfarin may need to be reduced.
when should warfarin be taken?
once daily, usually in the evening
what is the effect of hyperthyroidism on warfarin?
Hyperthyroidism increases the metabolism of clotting factors, which may require reduced doses of warfarin. Conversely, increased warfarin requirements have been seen in hypothyroid patients or those given carbimazole.
how long does the pharmacological effects of warfarin take to peak?
The peak pharmacological effect of warfarin takes several days to develop because of the time taken for the degradation of pre-formed carboxylated clotting factors.
Therefore monitor INR 4-7 days after dose changes
name some contraindications of warfarin?
Hypersensitivity
Haemorrhagic stroke
Clinically significant bleeding
Pregnancy (especially first and third trimester)
Severe liver disease
Severe renal impairment
Within 72 hours of major surgery, with severe
risk of bleeding
Concomitant drug treatments where interactions
may lead to a significantly increased risk of bleeding
Within 48 hours post-partum
what is the effect of amiodarone on warfarin?
It potentiates the anticoagulant effect of warfarin. Owing to the long half-life of amiodarone, these effects may peak between 2-7 weeks and persist long after amiodarone is stopped. Amiodarone induced thyrotoxicosis may also alter the INR in patients taking warfarin.
what is the effect of ibuprofen on warfarin?
although the anticoagulant effect of warfarin is not altered by ibuprofen, there is an increased risk of bleeding due to gastrointestinal irritation. The risk of gastrointestinal haemorrhage is increased.
what should patients avoid drinking when on warfarin therapy?
cranberry juice, grapefruit juice
high alcohol intake
mx of a raised INR?
- Stop warfarin or reduce the dose.
- Reverse anticoagulation if necessary (e.g. phytomenadione- vitamin K). Prothrombin complex concentrate may be required in some patients (specialist advice only).
- Investigate cause (e.g. dose, drug-interaction, adherence, patient education).
- Consider risk/benefit of continuing treatment.
what is the prescription unit of warfarin?
milligram
what is the mechanism of action of digoxin?
Digoxin is a cardiac glycoside. It increases the force of myocardial contraction and reduces conductivity within the atrioventricular node.
Digoxin is indicated for the management of heart failure and supraventricular arrhythmias.
how is digoxin monitored?
Plasma-digoxin concentration
Renal Function
Electrolytes- Hypokalaemia increases the risk of toxicity, as the myocardium is more sensitive to the effects of digitalis toxicity.
what is the effect of verapamil on digoxin?
When prescribed at a dose of 160 mg daily, verapamil can increase plasma digoxin levels by up to 40%. Verapamil reduces the renal and biliary clearance of digoxin. There is potential for additive bradycardia and heart block. An initial dose reduction of digoxin of 30 to 50% is recommended if this drug is added.
symptoms of digoxin toxicity?
anorexia N&V&D General malaise Weakness Palpitations Syncope Confusion Hallucinations Blurred vision Arrhythmias The risk of toxicity increases as plasma-digoxin concentration exceeds 2.0 micrograms/litre (2.6 nmol/litre). Toxicity is more likely in patients with hypokalaemia and in older adults.
management of digoxin toxicity?
- Stop digoxin.
- Measure plasma-digoxin concentration immediately if features of severe toxicity.
- Obtain information regarding the dose and timing of the last dose as this is useful when interpreting the level.
- Measure urea, electrolytes, potassium and creatinine and correct any disturbances.
- Monitor pulse, blood pressure and cardiac rhythm.
- Stop any drug treatments that may affect electrolyte balance or the clearance of digoxin.
what is the effect on hypokalaemia on digoxin?
Hypokalaemia, hypomagnesaemia, hypercalcaemia, alkalosis, hypoxia and hypothyroidism can all predispose patients to digoxin toxicity. Electrolyte abnormalities should be treated immediately.
how long does it take for digoxin to achieve full effect after a dose change?
A change in the steady-state plasma-digoxin concentration will not be seen for between 8 to 10 days following a change in dose. In renal failure it could take up to 21 days to reach steady-state concentration.
when should lithium levels be measured after starting a new dose?
Serum-lithium concentration should be measured 12 hours post-dose after at least four days.
what drug do you need to be brand specific when prescribing?
lithium
how often should serum lithium concentrations be monitored?
every 3 months
what parameters need to be monitored in lithium treatment?
Cardiac function- ECG regularly
TFTs- every 6 months, can cause hypothyroidism
Renal function- every 6 months (renally excreted)
Calcium- every 6 months, can cause hypercalcaemia
BMI- every 6 months, can cause weight gain
Serum lithium concentration
what can cause lithium toxicity?
Dose: the patient’s dose may be too high.
Dehydration: dehydration puts the patient at risk of toxicity, as elimination of lithium from the body is reduced.
Concomitant therapy: other drugs can increase the risk of toxicity, usually due to an effect on electrolyte balance and renal function.
Deterioration in renal function
features of severe lithium toxicity?
convulsions, coarse hand tremor, hypotension, dehydration, renal failure, electrolyte imbalances, and coma.
drugs that can interact with lithium, due to affecting renal elimination?
ACE inhibitors
Diuretics
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Sodium containing compounds (e.g. Movicol®)- decrease lithium conc
If you have to have concomitant drug therapy to lithium, how often should you be measuring drug levels?
weekly
indications for methotrexate?
Malignant disease
Psoriasis
Rheumatic disease
Crohn’s disease
typical dosing of methotrexate?
The starting dose is typically 7.5-15 mg once weekly.
The maximum dose generally does not exceed 25 mg once weekly for non-cancer treatment.
Folic acid is often (but not always) prescribed with methotrexate to reduce the adverse effects associated with folate deficiency. The recommended dose is 5 mg once weekly, prescribed on a different day to the methotrexate dose
monitoring needed for methotrexate therapy?
FBC, LFT, renal function
The BNF recommends that the full blood count, LFT and renal function should be monitored before treatment is initiated, then every 1-2 weeks until therapy has stabilised.
Monitoring is recommended every 2-3 months thereafter.
A chest X-ray is recommended on initiation. If symptoms of pulmonary toxicity emerge, the X-ray should be repeated.
signs and symptoms of methotrexate toxicity?
Lymphopenia Thrombocytopenia Pallor Nausea Vomiting Gastrointestinal bleeding Dysuria/anuria
what conditions can predispose methotrexate toxicity?
Hypoalbuminaemia
Folate deficiency
Concomitant drug treatments prescribed that reduce the elimination of methotrexate (e.g. NSAIDs)
Ascites or effusions which can act as a depot as methotrexate distributes well into tissue fluid
mx of methotrexate toxicity?
- STOP methotrexate
- Consult a haematologist/toxicologist
- Give folinic acid rescue therapy
common drug interactions with methotrexate?
aspirin- reduces elimination ciprofloxacin- reduces elimination clozapine- increase risk agranulocytosis steroids penicillins- reduce elimination NSAIDS- reduce elimination Trimethoprim- folate antagonist, don't prescribe
when should methotrexate therapy be omitted?
Acute illness, infection, and acute renal failure.
complications of methotrexate therapy?
Methotrexate can be associated with pneumonitis, infection, cytopenia, acute liver dysfunction, and serious haematological toxicity. When in doubt, seek senior support.
