Medication-induced problems

 Background
12% of all A&E visits and 7.1% of hospital admissions
35% of drug-related visits are 65+ year old
Medication involved: antibiotics (esp. paediatrics), anticoagulants (15% in elderly), opioids, NSAIDs,
diabetic agents

1. Medication-induced fever
 Characteristics
a. Diagnosis of exclusion
b. Duration between onset of symptoms and initiation of new drugs are often unhelpful
Can be significantly lagged
Highly variable and fluctuating (Median time of onset is 8 days, from 24 hours to months)
c. Upon discontinuation of the drugs, fever will reside usually in 3-4 days.

 Mechanisms & Common agents:

a. Hypersensitivity reactions (Fever can be the only manifestation in mild allergic reactions)
b. Altered thermoregulatory mechanisms
Levothyroxine, anticholinergics (e.g., atropine), TCAs
c. Reaction to administration
Vancomycin, amphotericin, chemotherapy, recreational drugs
d. Others
Anticonvulsants: Carbamazepine, phenytoin, phenobarbital, primidone
Onset often 5-6 days after initiation
Antimicrobials: Beta-lactams, sulfonamides, nitrofurantoin
Especially when used long term for acnes
Allopurinol
Risk factors: High dose, Renal impairment, HLA-B 5801 (Han-Chinese & Portugese)
Accompany with hepatotoxicity, renal impairment severe rash, eosinophilia
Chemotherapy
Heparin (but not LMWH)
e. Disease states
Malignant hyperthermia from succinylcholine
Neuroleptic syndrome
Serotonin syndrome

 High-risk patients:
a. Elderly
b. HIV
c. Cystic fibrosis
d. Many comorbidities

 Management
Discontinuation one drug at one time at the A&E department
Follow-up with primary physician days later
2. Medication-induced thrombocytopenia (Low platelet count)
 Characteristics
a. Less common in children
b. Onset within 2 weeks
c. Severe to dropped <20000uL (for HIT, less severe to <60000uL)
Bleeding risk is highest when <50000uL but there is poor correlation

 Classification
a. Immune-related: Medications
Antibiotics, statins, NSAIDs, antiepileptics, paracetamol, furosemide, amiordarone, haloperidol,
mirtazapine, chemotherapy agents
b. Non-immune-related
Bone marrow suppression
Chemotherapy or antibiotics
c. Heparin-induced Thrombocytopenia (HIT)

 Diagnosis
a. Do not attempt antibody testing – Too slow to get results
b. Never rechallenge – Very risky

 Pharmacist role
1. Identification of causative agents
2. Provide alternatives
3. Bleeding management options
4. Inform patients on positive prognosis and timeline
Platelet count increase in 1-2 days, return to normal in 7-8 days
Unless renal or hepatic impairment
5. House-keeping issues
Add drug to allergy list
Educate on avoidance of medications and complementary medicines

3. Medication-induced pancreatitis
 Characteristics
a. Only 0.3-2% of pancreatitis cases, but is increasing
b. No distinguishing clinical features: Variable onset from different medications

 Causes
a. Obstruction of common bile duct by stones (common)
b. Alcohol abuse (common)
c. Medications (rare, 1%; except in HIV patients, 40%)
4. Medication-induced rhabdomyolysis
 Characteristics
a. Most commonly caused by physical injury
b. Major concern: Acute kidney injury (50%)

 Risk factors
a. Female sex
b. Renal or hepatic impairment -> Accumulation of ascending drug
c. Increasing age
d. High dosages of medications
e. Diabetes
f. Illicit substance uses (34%)
g. Prescription medications (11%): Antipsychotics, Statins, SSRI

 Treatment (hydration and perfusion)

a. Normal saline 100-200mL/hour
b. Bicarbonate infusion: No hypocalcemia, pH >7.5, Serum bicarbonate <30
c. Furosemide: If fluid overload
d. Mannitol: No evidence, not used in Hong Kong