High Risk Drugs Flashcards
(146 cards)
1
Q
Is loading dose usually required with drugs with short or long half-life?
A
Drugs with long half-lives will take longer to reach steady state, therefore, require a loading dose to rapidly achieve target concentration for acute therapeutic response.
2
Q
What is the indication of amiodarone?
A
Treatment of arrhythmias - but usually is not first line - it is used when other treatments have failed or is contra-indicated. (Initiated in hospital under specialist supervision).
3
Q
What is the half life of amiodarone?
A
about 50 days
Loading doses may be required
4
Q
What is the usual oral dose of Amiodarone?
A
200 mg 3 times a day for 1 week, then reduced to 200 mg twice daily for a further week, followed by maintenance dose, usually 200 mg daily or the minimum dose required to control arrhythmia.
5
Q
What are the monitoring requirements for Amiodarone?
A
- Thyroid function
- Liver function
- Serum potassium
- Chest X-ray
- ECG (with intravenous use)
6
Q
What are the warning signs to be aware of with amiodarone?
A
- signs and symptoms of hypo or hyperthyroidism
- impaired vision (optic neuritis, optic neuropathy)
- photophobia, dazzled by headlights at night (corneal micro deposits)
- progressive shortness of breath or cough (pneumonitis, pulmonary toxicity)
- clinical signs of liver disease e.g. jaundice
- Neurological effects of tremor, peripheral neuropathy (e.g. develop numbness and tingling in hands and feet)
- phototoxic skin reactions e.g. burning sensation followed by erythema, and persistent slate grey skin discoloration on light-exposed areas.
7
Q
What advise should be given to people taking amiodarone?
A
- Advise patient to shield skin from direct sunlight and for several months after stopping treatment or to use a wide-spectrum sunscreen
- warn drivers that they may be dazzled by headlights at night
- warn patients that the clinical effects may occur up to a year after stopping the medicine.
8
Q
As amiodarone has a long half-life, what advice should be given about drug interactions?
A
There is a potential for drug interactions for several weeks to months after treatment has been stopped.
9
Q
Which drugs plasma concentration is increased when given with amiodarone?
A
Coumarins, dabigatran, digoxin, flecainide, phenindione and phenytoin.
10
Q
Which drugs when given with amiodarone increases the risk of ventricular arrhythmias?
A
amisulpride, atomexetine, chloroquine, citalopram, disopyramide, escitalopram, haloperidol, hydroxychloroquine, levofloxacin, lithium, mizolastine, mefloquine, mocifloxacin, phenothiazine, pimozide, quinine, sulpride, telithromycin, tolterodine tricyclics
11
Q
When amiodarone is given with either beta blockers, diltiazem or verapamil, what is there an increased risk of?
A
Increased risk of bradycardia, AV block and myocardial depression.
12
Q
Interaction between amiodarone and simvastatin?
A
Increased risk of myopathy
13
Q
What are the common indications of digoxin?
A
1) In atrial fibrillation (AF) and atrial flutter, digoxin is used to reduce the ventricular rate. However, a β-blocker or non-dihydropyridine calcium channel blocker is usually more effective.
2) In severe heart failure, digoxin is an option in patients who are already taking an ACE inhibitor, β-blocker and either an aldosterone antagonist or angiotensin receptor blocker. It is used at an earlier stage in patients with co-existing AF.
14
Q
What is the mechanism of action of digoxin?
A
Digoxin is negatively chronotropic (it reduces the heart rate) and positively inotropic (it increases the force of contraction).
In AF and flutter its therapeutic effect arises mainly via an indirect pathway involving increased vagal (parasympathetic) tone.
- this reduces conduction at the atrioventricular (AV) node, preventing impulses from being transmitted to the ventricles, thereby reducing ventricular rate.
15
Q
In heart failure what is the mechanism of digoxin?
A
In heart failure, it has a direct effect on myocytes through inhibition of Na+/K+ ATPase pump, causing Na+ to accumulate in the cell. As cellular extrusion of Ca2+ requires low intracellular Na+ concentrations, elevations of intracellular Na_ causes Ca2+ to accumulate in the cell, increasing contractile force.
16
Q
What is digoxin dose decided by?
A
Dose is decided by ventricular rate at rest and persistent rate shouldn’t fall under 60.
17
Q
Which patients do not require a loading dose?
A
Patients with heart failure and sinus rhythm don’t require a loading dose
18
Q
Does digoxin have a long half life?
A
Yes so it is given once daily
19
Q
Which type of impairment is most important in deciding the dose of digoxin?
A
Renal function
20
Q
What can digoxin side effects be mixed with?
A
It can be hard to distinguish between side effect and deteriorating heart condition.
21
Q
What range of digoxin does toxicity progress in?
A
Through the range 1.5mcg-3mcg/L.
22
Q
Is regular monitoring required when on digoxin?
A
No - unless toxicity is suspected
23
Q
What are the side effects of digoxin?
A
- Arrhythmias
- blurred vision
- Yellow vision
- conduction disturbances
- dizziness
- eosinophilia
- nausea and vomiting
- rash
24
Q
When switching from IV digoxin to oral what dose change is needed?
A
Increase the dose by 20-33% so plasma concentration can be maintained
25
Which conditions is digoxin contraindicated in?
- constructive pericarditis
- hypertrophic cardiomyopathy
- intermittent heart block
- myocarditis
- second-degree AV block
- supraventricular arrhythmias e.g. wolff-parkinson syndrome.
26
Which patients should digoxin be used with caution?
Those with hyperkalaemia, hypokalaemia
27
Which electrolyte imbalance can potentiate toxicity of digoxin?
- hypokalaemia
- hypomagnesaemia
- hypercalcaemia
28
With digoxin what heart rate should be maintained?
at greater than 60 beats per minute
29
What should be monitored for those on digoxin treatment?
- serum electrolytes (K+, Mg2+ and Ca2+).
- renal function
- heart rate
30
What is the major route of elimination for digoxin?
- renal excretion; hepatic metabolism to active metabolites.
31
What are the warning signs of digoxin?
- Cardiac e.g. arrhythmias, heart block
- Neurological e.g. weakness, lethargy, dizziness, headaches, mental confusion, psychosis
- Gastrointestinal e.g. anorexia, nausea, vomiting, diarrhoea, abdominal pain
- Visual e.g. blurred and/ or yellow vision
32
Does digoxin + st John's wort increase or decrease plasma concentration of digoxin?
Decrease
33
What other interactions is there to know of with digoxin?
Concomitant adminstration of acetazolamide, amphoterecin, loop diuretics or thiazides and related diuretics can cause hypokalaemia that increases the risk of cardiac toxicity and digoxin toxicity.
34
Which drugs increase plasma concentration of digoxin?
- alprazolamiodarone
- ciclosporin
- diltiazem
- itrazonazole
- lercanidipine
- macrolides
- mirabegron
- nicardipine
- nefidipine
- quinine
- spironolactone
- verapamil
35
How long does it taken for effect of digoxin with IV / oral?
```
IV = 30 mins
Oral = about 2 hours
```
36
When rapid effect is needed, what is required?
A loading dose
37
What is the usual maintenance dose of digoxin?
125-250 micrograms
38
Digoxin with or without food?
Can be taken with or without food,
39
What can therapetic doses of digoxin cause on the ECG?
should note that therapeutic doses of digoxin can cause ST-segment depression (the ‘reverse tick’ sign) on the ECG. This is an expected effect and does not signify toxicity.
40
Why is digoxin rarely used now on its own for AF?
Because digoxin’s effect on ventricular rate in AF relies on parasympathetic (‘rest and digest’) tone, it tends to be lost during stress and exercise. Digoxin is therefore now rarely used on its own for AF, although it may be an option in sedentary patients.
41
For digoxin assay when should blood be taken?
At least 6 hours after the dose.
42
During digoxin therapy, it is essential to monitor serum potassium levels because....?
- Low potassium levels increase the chance of digoxin toxicity
43
Mrs. Chin is undergoing digoxin therapy and begins to complain of headache and studies revel a dysrhythmia. What is happening with this patient?
Digoxin toxicity
44
Mr. Ferris also complains of constipation. He complains that if he were allowed to eat his high fiber bran as often as he used to, he wouldn't be constipated. What teaching should the nurse provide to Mr. Ferris?
Food high in fiber bind to digitalis and make it less effective
45
Which class/ type of drug is azathioprine?
Anti-metabolite/ Immunosuppressant
46
What are the main indications of azathioprine?
1) Maintenance of remission of Chron's disease and ulcerative colitis (UC)
2) As a disease modifying agent in rheumatoid arthritis and autoimmune conditions not responding to corticosteroids or other standard treatments
3) To prevent organ rejection in transplant recipients
47
Is azathioprine pharmacologically active?
Azathioprine is a pro-drug. this means that itself it is not pharmacologically active but on metabolism it is converted to substances that are.
48
What is the main metabolite that azathioprine is converted to?
6-mercaptopurine which is further metabolised to active substances.
49
What is the MOA of azathioprine?
The active metabolites inhibit the synthesis of purines (notably the nucleosides adenine and guanine) and therefore inhibit DNA and ribonucleic acid (RNA) replication.
- Whereas most cells can 'salvage' or 'recycle' purines, lymphocytes are dependent on purine synthesis and so are particularly affected by azathioprine metabolites.
50
Which enzymes does the metabolism and elimination of azathioprine involve?
- Xanthine oxidase
- Thiopurine methyltransferase (TPMT)
The activity of the latter is reduced or absent in some individuals.
51
What is the most serious dose related effect of azathiopurine?
- Bone marrow suppression - which results most significantly in leukopenia and an increased risk of infection.
52
What may results in resolving bone marrow suppression associated with azathioprine?
- A reduction in dose or temporary break in therapy may resolve this.
53
With Azathioprine nausea is common, what can be done to reduce this?
By dividing the daily doses
54
What side effects (hypersensitivity) can occur with azathioprine?
- diarrhoea
- vomiting
- rash
- fever
- myalgia
- hypotension
- pancreatitis
55
What are some rare but serous side effects of azathioprine?
- veno-occlusive disease
- hepatoxicity
- increased risk of some tumours such as lymphoma
56
What should be performed before starting therapy with Azathioprine?
TPMT performing should be performed before starting therapy as it may help identify those at risk.
57
What is the effect of TPMT activity on prescribing azathioprine?
Absent TPMT activity = should not prescribe azathioprine
Reduced TPMT activity = treated only by specialist
58
What is the effect of Azathioprine dose in hepatic and renal impairment?
Dosage should be reduced
59
Is azathioprine teratogenic?
It is teratogenic in animal studies although the effects in humans are less clear.
60
Can Azathioprine be used in pregnancy?
In general, treatment should not be initiated in pregnancy but may continue in those already established on treatment where the benefits outweigh the risks of stopping (e.g. transplant recipients).
61
Which other drugs when taken with azathioprine increase the risk of infection?
When used with other suppressants such as corticosteroids, although co-prescription may be unavoidable in the condition indicated.
62
Why shouldn't azathioprine be given with allopurinol?
Azathioprine should not be prescribed with xanthine oxidase inhibitors (such as allopurinol), as they reduce azathioprine metabolism and increase the risk of toxciity.
63
Why does azathioprine and trimethoprim interaction result in increased risk of leukopenia?
The risk of leukopenia is increased when prescribed with other drugs that are myelosuppressive or have effects on purine synthesis (e.g. trimethoprim).
64
What is the effect of azathioprine on warfarin?
Azathioprine may reduce the effect of warfarin necessitating dosage adjustments.
65
What basis is the dose of azathioprine based on?
- Weight basis
66
What administration form is preferred with azathioprine?
- Oral treatment is preferred.
| - IV preparations are available but are an irritant to blood vessels.
67
Where IV use of azathioprine is unavailable what should the drug be diluted?
Yes (e.g. to 100-250ml) and given by infusion (e.g. over 60min)
68
When on azathioprine treatment patients should report which symptoms?
Seek urgent medical advice if they develop sore throat or fever (infection), bruising or bleeding (low platelet count) or rash, diarrhoea, vomiting or abdominal pain (hypersensitivity).
69
What monitoring requirements are the for Azathioprine?
FBC
weekly for first for weeks after initiation or dose alteration and 3-monthly thereafter.
Blood tests and monitoring for signs of myelosuppression are essential in long-term treatment.
70
What is the risk of azathioprine and ACE inhibitors?
- increased risk of anaemia and/or leucopenia
71
What is the effect of Azathioprine on the effect of anticoagulants?
- Anticoagulant effect of coumarins reduced
72
Can people on azathioprine treatment get live vaccines?
No - as with azathioprine there is an increased risk of generalised infection
73
When is azathioprine contraindicated?
- absent TPMT activity
| - Very low TPMT activity
74
When is azathioprine dose reduced?
- reduce in elderly
| - in reduced TPMT activity
75
What should be done if a patient is experiencing a hypersensitivity to azathioprine?
Hypersensitivity reactions (including malaise, dizziness, vomiting, diarrhoea, fever, rigors, myalgia, arthralgia, rash, hypotension and renal dysfunction) call for immediate withdrawal.
76
What are the indications of theophylline?
- Chronic asthma
- Reversible airways obstruction
- Severe asthma
-
77
What is the brand name of theophylline modified release tabs?
Uniphyllin Continus
78
What class of drug does theophylline belong to?
Xanthines
79
What is the mechanism of action of theophylline?
Theophylline relaxes the smooth muscles located in the bronchial airways and pulmonary blood vessels. It also reduces the airway responsiveness to histamine, adenosine, methacholine, and allergens.
In other words, It works by relaxing the muscles around the airways so that they open up and you can breathe more easily. It also decreases the lungs' response to irritants.
80
Where is theophylline metabolised?
Theophylline is metabolised in the liver.
81
Is plasma concentration increased or decreased in heart failure, hepatic impairment, and in viral infections?
concentration is increased
82
Is plasma-theophylline concentration increased or decreased in smokers, and by alcohol consumption?
Concentration is decreased
83
Why is difference in the half life of theophylline important?
It is important because the toxic dose is close to the therapeutic dose.
84
What is the therapeutic range of theophylline?
10 to 20mg/L
(although a plasma concentration theophylline concentration of 5 to 15mg/L may still be effective)
Loaded doses may be required
85
What monitoring is required for theophylline?
- serum potassium
| - plasma theophylline concentration
86
Why should plasma concentrations be monitored for those on theophylline?
Potentially serious hypokalaemia may result from beta2-agonist therapy. Particular caution is required in severe asthma, because this effect may be potentiated by concomitant treatment with theophylline and its derivatives, corticosteroids, and diuretics, and by hypoxia.
Therefore, plasma concentrations should be monitored.
87
What are the side effects of theophylline?
```
headache,
nausea, stomach upset, or vomiting.
not sleeping well.
increased heart rate.
skin rash.
seizures.
weight loss
fatigue
muscular weakness
```
88
What are the signs of theophylline overdose (toxicity)?
```
Vomiting
Agitation
Restlessness
Tachycardia
Hyperglycaemia
Pupil Dilation
Severe Hypokalaemia
```
89
In which conditions is theophylline to be given with caution
```
Cardiac arrhythmias
Elderly
Epilepsy
Hypertension
Peptic ulcer
```
Frequent courses of antibiotics and/or oral corticosteroids
90
What are the symptoms of uncontrolled asthma?
- Cough
- Wheeze
- Tightness of chest
91
If a patient on theophylline stops smoking then they should see their doctor?
Yes as smoking is an inducer (it reduces concentration of theophylline - increases metabolism) and stopping means there will be more of the drug available
92
For theophylline patient should remain on the same brand?
Yes patient should stay on the same brand of medicine and recommend that the patient always checks when collecting their medicines from a pharmacy and when taking the medicine
(The rate of absorption from modified release preparations can vary between brands).
93
What may result from beta 2 agonist therapy? (hint - electrolyte inbalace)
- Potentially serious hypokaelaemia
94
Which drugs if taken with theophylline can increase the concentration of theophylline?
- Diltiazem
- Cimetidine
- Ciprofloxacin
- Erythromycin
- Oestrogens
- Fluvoxamine
- Verapamil
95
With which class of drugs if given with theophylline there is an possible increased risk of convulsion?
Quinolones
96
Which drugs if taken with theophylline can decrease the concentration of theophylline?
- Carbamazepine
- Primidone
- Phenobarbital
- Phenytoin
- Ritonavir
97
How often or when is theophylline concentrations measured?
5 days after starting oral treatment and 3 days after any dose adjustment
98
When a blood sample of theophylline is needed when should this be taken?
A blood sample should be taken usually 4-6 hours after an oral dose of MR preparation
99
Can theophylline be taken in pregnancy or breast-feeding?
Can be taken normally during pregnancy but important asthma is well controlled during pregnancy.
(Neonatal irritability and apnoea has been reported)
- present in breast milk - irritability in infant. MR preparation preferred (theophylline can be taken as normal during breast-feeding)
100
When dispensing a prescription for theophylline for a modified release oral preparation if a brand name has not been specified then what should the pharmacist do?
The pharmacist should contact the prescriber and agree the brand to be dispensed
Additionally, it is essential that a patient discharged from hospital should be maintained on the brand on which that patient was stabilised as an in-patient.
101
What is the drug action of methotrexate?
Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines
102
What are the indications of methotrexate?
- Severe Crohn's disease
- Maintenance of remission of severe Chron's disease
- Moderate to severe active rheumatoid arthritis
- Neoplastic disease
- Severe psoriasis unresponsive to conventional therapy (specialist use only)
103
Is methotrexate taken daily or weekly?
Weekly (once a week on the same day each week)
104
What are the contraindications of methotrexate?
- Active infection
| - Immunodeficiency
105
What signs and symptoms require referral to doctor when on methotrexate?
- Blood disorder (sore throat, bruising, mouth ulcers)
- Liver toxicity (Nausea, vomiting, abdominal discomfort, dark urine)
- Respiratory effects (Pulmonary toxicity, shortness of breath)
- Photosensitivity
- Stomatitis
106
When on methotrexate what does a drop in blood count require?
Blood count - drop in white cell or platelet count requires immediate withdrawal
107
How long is contraception required for methotrexate?
Effective contraception needed during treatment and 6 months after for both male and female
108
Can you take methotrexate while pregnant or breastfeeding?
No avoid as teratogenic and present in breast milk
109
What signs could indicate methotrexate induced bone marrow suppression?
Sore throat, bruising, mouth ulcers
110
What signs could indicate liver toxicity?
- nausea, vomiting, yellowing of the skin and whites of the eyes, fatigue, loss of appetite
111
What should be monitored for methotrexate?
Reports blood dyscrasias (including fatalities) and liver cirrhosis with low-dose methotrexate, therefore monitor:
- Full blood count
- Liver Function Tests
- Renal Function
112
How often is the parameters monitored for methotrexate?
Repeat 1-2 weeks until therapy stabilised,
Thereafter, patients should be monitored every 2-3 months
113
What is the antidote to methotrexate overdose?
Folinic acid (as calcium folinate)
114
Which other drug is usually given along side methotrexate?
Folic acid - to reduce side effects experienced by methotrexate such as nausea
This is given daily jus not on the day that folic acid is taken
115
What additional thing should the pharmacy provide for patients on methotrexate?
Methotrexate treatment booklet
116
Patients on methotrexate should be advised to avoid OTC preparations containing which drugs?
- ibuprofen (NSAIDs) and aspirin
117
Are patients that are on methotrexate recommended to get annual flu vaccine?
Yes - but should avoid live vaccines
118
There is an increased plasma concentration of methotrexate and hepatoxicity if it is used with which other drug (that can be used for psoriasis)?
- with Acitretin
| Avoid this with methotrexate
119
What is the effect of taking NSAIDS or penicillins with methotrexate (why are these advised to be avoided with methotrexate)?
- excretion of methotrexate is reduced
120
There is an increased risk of toxicity when methotrexate is given with which drugs?
- Ciprofloxacin
- Doxycycline
- Tetracycline
- Sulfonamides
- Ciclosporin
- Proton pump inhibitors
- Leflunomide
121
There is an increased risk of haematological toxicity when methotrexate is given with which drugs?
Sulmathoxazole (co-trimoxazole) or
Trimethoprim
(All reduce dihydrofolate/ folate)
122
What route can methotrexate be given?
Weekly dose
– For chemo = PO or IV or intrathecally
– For non-cancer (e.g. arthritis) = IM or SC
123
What are some of the side effects of methotrexate?
anaemia; appetite decreased; diarrhoea; drowsiness; fatigue; gastrointestinal discomfort; headache; increased risk of infection; leucopenia; nausea; oral disorders; respiratory disorders; skin reactions; throat ulcer; thrombocytopenia; vomiting
Myelosupression, mucositis and rarely pneumonitis
124
Can methotrexate be used in severe renal impairment?
No avoid; excreted mainly via kidneys
125
Can methotrexate be used in severe hepatic impairment?
No avoid
126
Administration of which drug following methotrexate administration helps to prevent methotrexate induced mucositis or myelosuppression?
Folinic acid
127
Do you need to withdraw if stomatitis or diarrhoea develops when on methotrexate?
Yes - May be first sign of gastro-intestinal toxicity
128
Pulmonary toxicity is another problem with methotrexate especially in rheumatoid arthritis - what are the signs that can suggest this?
- Patient to seek medical attention if dyspnoea, cough or fever develops)
- Discontinue if pneumonitis suspected
129
What are the cautions listed on the BNF for methotrexate?
Photosensitivity—psoriasis lesions aggravated by UV radiation (skin ulceration reported); dehydration (increased risk of toxicity); diarrhoea; extreme caution in blood disorders (avoid if severe); peptic ulceration (avoid in active disease); risk of accumulation in pleural effusion or ascites—drain before treatment; ulcerative colitis; ulcerative stomatitis
130
What are the contra-indications of methotrexate?
Active infection; ascites; immunodeficiency syndromes; significant pleural effusion
131
What is the purpose of folic acid alongside methotrexate?
Give folic acid to reduce side-effects. Folic acid decreases mucosal and gastrointestinal side-effects of methotrexate and may prevent hepatotoxicity; there is no evidence of a reduction in haematological side-effects.
132
What is the indication of carbamazepine?
- Focal seizures
- primary and secondary generalised tonic-clonic seizures
- Trigeminal neuralgia
- Prophylais of bipolar disorder unresponsive to lithium
- Adjunct in acute alcohol withdrawal
- Diabetic neuropathy (Unlicensed)
133
Are brands interchangable for carbamazepine?
No- need to give same band e.g. tegretol
134
Is carbamazepine a drug with a narrow therapeutic index?
Yes
135
What is the therapeutic range of carbamazepine?
4-12mg/L (20-50micromol/L)
136
What monitoring does manufacturer recommend for carbamazepine?
FBC, Liver function and renal function
(but evidence of practical value is uncertain for this)
Plasma drug concentration
137
What treatment cessation should be noted?
When stopping treatment with carbamazepine for bipolar disorder, reduce the dose gradually over a period of at least 4 weeks
138
What signs and symptoms should patients report immediately?
- reports of blood, liver, or skin disorders and advised to seek immediate medical attention if symptoms such as fever, rash, mouth, ulcers, bruising or bleeding develop.
139
Which types of seizures may be exacerbated by carbamazepine?
Myoclonic and absence seizures
140
For patients taking carbamazepine, which patients may benefit from a Vit D supplementation?
- If immobilised for long periods, have inadequate sun exposure or inadequate calcium
141
What is the antidote to carbamazepine over dose?
There is no specific antidote. Multiple-dose activated charcoal and hemodialysis are the main treatment for carbamazepine intoxication.
142
Can carbamazepine be used in pregnancy?
An increased risk of major congenital malformations has been seen with carbamazepine.
Plasma-drug concentration should be monitored and may be maintained on the lower side of the therapeutic range provided seizure control is maintained.
143
Can you breastfeed while taking carbamazepine?
Yes - amount probably too small to be harmful
144
What are some of the common side effects of carbamazepine?
```
Allergic skin reactions;
• aplastic anaemia;
• ataxia;
• blood disorders;
• blurring of vision;
• dermatitis;
• dizziness;
• drowsiness;
• dry mouth;
• eosinophilia;
• fatigue;
• haemolytic anaemia;
• headache;
• hyponatraemia (leading in rare cases to water
intoxication);
• leucopenia;
• nausea;
• oedema;
• thrombocytopenia;
• unsteadiness;
• urticaria;
• vomiting
```
145
Which side effects may be dose-related for carbamazepine?
Some side-effects (such as headache, ataxia,
drowsiness, nausea, vomiting, blurring of vision,
dizziness, unsteadiness, and allergic skin reactions) are
dose-related, and may be dose-limiting.
These side-effects are more common at the start of
treatment and in the elderly.
146
What pre-treatment screening may be beneficial for carbamazepine?
Test for HLA-B*1502 allele in individuals of Han Chinese or Thai origin (avoid unless no alternative—risk of Stevens-Johnson syndrome in presence of HLA-B*1502 allele).
