Adverse Drug Reactions and Pharmacovigilance
An adverse drug reaction (ADR) is any undesired, noxious, or unintended response to a medicine that occurs at doses used for prophylaxis, diagnosis, or therapy. Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. In South Africa, where the Medicines and Related Substances Control Act (Act 101 of 1965, as amended) governs medicines safety, and where the South African Health Products Regulatory Authority (SAHPRA) operates the national pharmacovigilance programme, understanding ADRs and pharmacovigilance systems is a professional and legal obligation for pharmacists.
The SAPC examination tests candidates on ADR classification, mechanisms, reporting systems, medication safety principles, and clinical management. This topic is closely linked to drug interactions (pharma-008) and pharmacokinetics (pharma-003 through pharma-007).
Classification of Adverse Drug Reactions
ADRs are broadly classified using two systems: the historical Type A–F classification, and the more recent Rawlins-Thompson classification.
Type A (Augmented) Reactions
Type A reactions are predictable, dose-dependent extensions of the drug’s pharmacological effect. They are common (accounting for approximately 80–90% of all ADRs) and often reversible upon dose reduction or drug withdrawal.
Characteristics:
- Result from exaggerated pharmacological effect
- Dose-dependent (higher dose = more severe reaction)
- Predictable based on known pharmacology
- Relatively common
- Often reversible
Examples:
- β-blocker-induced bradycardia (exaggerated β-blockade)
- ACE inhibitor-induced cough (exaggerated bradykinin accumulation)
- Warfarin-induced bleeding (exaggerated anticoagulation)
- NSAIDs-induced gastric erosions (exaggerated prostaglandin inhibition)
- Morphine-induced respiratory depression (exaggerated CNS depression)
- Hypoglycaemia from sulfonylureas (exaggerated insulin secretion)
Management: Dose reduction, drug cessation, or addition of counteracting agent.
Type B (Bizarre) Reactions
Type B reactions are unpredictable, dose-independent, and not related to the drug’s known pharmacology. They are typically immunological or genetic in origin. Also called “idiosyncratic” reactions.
Characteristics:
- Unpredictable; no relation to dose
- Not related to known pharmacology
- Often severe and potentially fatal
- Require prior sensitisation or genetic predisposition
- Relatively rare (1–10% of ADRs)
Examples:
- Penicillin-induced anaphylaxis (IgE-mediated Type I hypersensitivity)
- Sulfonamide-induced Stevens-Johnson syndrome (SJS) (Type IV hypersensitivity, HLA-linked)
- Halothane-induced hepatitis (immune-mediated, rare but severe)
- Chloramphenicol-induced aplastic anaemia (bone marrow toxicity, genetic predisposition)
- Phenytoin-induced aromatic anticonvulsant hypersensitivity syndrome
- Carbamazepine-induced SJS/TEN — particularly associated with HLA-B*1502 allele (more common in some Asian populations; relevant for SA’s diverse population)
Management: Immediate drug withdrawal; supportive care; desensitisation may be possible for some drugs (e.g., insulin allergies).
Type C (Chronic) Reactions
Type C reactions are delayed or chronic effects occurring after prolonged drug use.
Characteristics:
- Develop after long-term use (months to years)
- Often irreversible
- Mechanism may involve adaptive biological responses
Examples:
- Corticosteroid-induced osteoporosis (chronic suppression of bone formation)
- NSAIDs-induced renal papillary necrosis (chronic analgesic nephropathy)
- Antipsychotic-induced tardive dyskinesia (dopamine receptor supersensitivity)
- Benzodiazepine dependence and withdrawal (chronic CNS adaptation)
- Retinol-induced hypervitaminosis A (chronic excessive dosing)
- Amiodarone-induced pulmonary fibrosis (chronic toxicity)
Type D (Delayed) Reactions
Type D reactions are delayed effects that may appear long after drug cessation. These include carcinogenicity and teratogenicity.
Characteristics:
- Appear after a long latency period
- May be irreversible
- Can affect future generations (teratogenicity)
Examples:
- Diethylstilboestrol (DES) — clear cell carcinoma of vagina in daughters of exposed mothers
- Thalidomide — phocomelia (severe limb malformations) in exposed foetuses
- Alkylating agents — secondary malignancies after cancer chemotherapy
- Clofibrate — increased mortality after long-term use (revealed in long-term studies)
- Hormone replacement therapy — increased risk of breast cancer with long-term oestrogen use
SA context: Thalidomide is strictly contraindicated in pregnancy in South Africa. SAHPRA requires a strict pregnancy prevention programme for all patients prescribed thalidomide (used for leprosy reactions, multiple myeloma).
Type E (End-of-treatment) Reactions
Type E reactions occur upon abrupt withdrawal or cessation of a drug after prolonged use. They result from physiological adaptation to the drug.
Characteristics:
- Occur when drug is stopped suddenly after long-term use
- Reflect physiological dependence/adaptation
- Can be life-threatening
Examples:
- Benzodiazepine withdrawal syndrome (seizures, anxiety, insomnia)
- Corticosteroid withdrawal (adrenal insufficiency, disease flare)
- Clonidine withdrawal (rebound hypertension)
- β-blocker withdrawal (rebound tachycardia, hypertensive crisis — particularly after myocardial infarction)
- Opioid withdrawal syndrome
- SSRIs/SNRIs withdrawal syndrome (discontinuation syndrome)
Management: Gradual taper rather than abrupt cessation; patient counselling at dispensing.
Type F (Failure of Therapy) Reactions
Type F reactions occur when drug therapy fails to produce its intended effect.
Characteristics:
- Includes all causes of therapeutic failure
- May be due to resistance, inadequate dosing, or interactions
Examples:
- Antibiotic resistance (failure of antimicrobial therapy)
- Antiepileptic drug resistance
- Inadequate warfarin effect due to CYP2C9 induction
- Contraceptive failure due to enzyme induction
Immunological Mechanisms of ADRs
Type I Hypersensitivity (Immediate/Anaphylactic)
IgE-mediated, occurring within minutes to hours of drug exposure.
Mechanism: Prior sensitisation → IgE antibody production → IgE binds to mast cells and basophils → drug (allergen) cross-links IgE → mast cell degranulation → histamine, leukotrienes, prostaglandins released.
Clinical features: Urticaria, angioedema, bronchospasm, hypotension, anaphylaxis.
Examples: Penicillin anaphylaxis, sulphonamide reactions, radiocontrast media reactions.
Management: Adrenaline (epinephrine) IM for anaphylaxis; antihistamines; corticosteroids; bronchodilators.
Type II Hypersensitivity (Cytotoxic/Antibody-Mediated)
IgG or IgM antibodies react with cell surface antigens or drugs adsorbed onto cell surfaces.
Mechanism: Antibodies directed against drug or drug-cell complex → complement activation or ADCC → cell destruction.
Clinical features: Haemolytic anaemia, thrombocytopenia, neutropenia.
Examples: Methyldopa-induced autoimmune haemolytic anaemia (AIHA); penicillin-induced haemolytic anaemia.
Type III Hypersensitivity (Immune Complex)
Soluble antigen-antibody complexes deposit in tissues → complement activation → inflammation.
Mechanism: Drug acts as antigen → antibody (IgG) forms immune complexes → complexes deposit in vascular beds → complement activation → inflammation and tissue damage.
Clinical features: Serum sickness (fever, urticaria, arthralgia, proteinuria), vasculitis, glomerulonephritis.
Examples: Serum sickness from antithymocyte globulin; drug-induced lupus (procainamide, hydralazine, isoniazid); Arthus reaction (localised immune complex vasculitis at injection site).
Type IV Hypersensitivity (Delayed/Cell-Mediated)
T-cell mediated; occurs 24–72 hours after exposure.
Mechanism: Drug or hapten-modified protein processed by APCs → sensitised T-cells → cytokine release → macrophage activation and tissue damage.
Clinical features: Contact dermatitis, maculopapular rash, SJS, TEN, DRESS (drug reaction with eosinophilia and systemic symptoms).
Examples:
- Topical antihistamines (contact dermatitis)
- Sulphonamides, anticonvulsants, allopurinol → SJS/TEN (strongly associated with HLA alleles)
- DRESS syndrome: aromatic anticonvulsants (phenytoin, carbamazepine), allopurinol, sulfonamides
SJS/TEN — clinical emergency: Stevens-Johnson Syndrome (SJS, <10% body surface area detachment) and Toxic Epidermal Necrolysis (TEN, >30% BSA detachment) are severe mucocutaneous reactions. Mortality rates: SJS 1–5%; SJS/TEN overlap 5–10%; TEN 25–30%. Causative drugs in SA: sulfonamides (including co-trimoxazole, widely used for PCP prophylaxis in HIV), anticonvulsants, allopurinol, NSAIDs. Management requires ICU/burn unit, withdrawal of causative agent, IVIG or ciclosporin.
Mechanisms of Common ADRs by Organ System
Cardiovascular ADRs
| ADR | Drug Class | Mechanism |
|---|---|---|
| QT prolongation | Antiarrhythmics (quinidine, sotalol), antipsychotics (thioridazine, haloperidol), fluoroquinolones, macrolides, domperidone | Block cardiac potassium channels (IKr) |
| Heart block | β-blockers, verapamil, diltiazem, digoxin | Negative chronotropic effect |
| Torsades de pointes | Class IA/III antiarrhythmics, drugs causing QT prolongation + hypokalaemia | Prolonged repolarisation |
| Fluid retention | NSAIDs, minoxidil, calcium channel blockers | Renal sodium retention, vasodilation |
| Hyper/hypotension | MAOIs + tyramine ( hypertensive crisis), sildenafil + nitrates (severe hypotension) | Interaction mechanisms |
Hepatotoxic ADRs
Acetaminophen (paracetamol) hepatotoxicity — prototype of metabolic activation: Paracetamol is metabolised primarily by glucuronidation (Phase II) and sulfation. A small fraction is oxidised by CYP2E1 to the toxic electrophile N-acetyl-p-benzoquinone imine (NAPQI). At therapeutic doses, NAPQI is detoxified by glutathione. In overdose, glutathione is depleted, NAPQI accumulates, and binds covalently to hepatocyte proteins → centrilobular necrosis.
Antidote: N-acetylcysteine (NAC), which replenishes glutathione and also directly scavenges NAPQI. Most effective when given within 8 hours of ingestion. In South Africa, paracetamol-containing products are widely available OTC; paracetamol overdose is a common cause of acute liver failure presenting to emergency departments.
Other hepatotoxic drugs:
| Drug | Type of Hepatotoxicity |
|---|---|
| Halothane | Direct hepatotoxicity (centrilobular) and immune-mediated hepatitis |
| Valproic acid | Microvesicular steatosis, fulminant hepatic failure |
| Isoniazid | Metabolic idiosyncratic (CYP2E1); risk factors: slow acetylators, alcoholism |
| Rifampicin | Cholestatic; potent enzyme inducer (may increase INH toxicity) |
| Methotrexate | Steatohepatitis (fatty liver), fibrosis |
| Antiepileptics (phenytoin, carbamazepine, phenobarbital) | Enzyme induction → hepatic injury |
| Statins (especially simvastatin) | Dose-dependent hepatotoxicity; monitoring LFTs recommended |
| Herbal medicines | Many traditional medicines cause hepatotoxicity; devil’s claw, comfrey, kava (banned in SA) |
Nephrotoxic ADRs
Aminoglycoside nephrotoxicity: Aminoglycosides (gentamicin, amikacin) are filtered at glomerulus and accumulate in proximal tubular cells via pinocytosis. They cause tubular necrosis through mitochondrial damage and free radical generation. Nephrotoxicity occurs in 10–20% of patients receiving aminoglycosides. Risk factors: prolonged therapy, elevated trough levels, pre-existing renal impairment, dehydration, concomitant nephrotoxins.
Monitoring: Serum creatinine and aminoglycoside peak/trough levels. SA therapeutic ranges: gentamicin peak 5–10 mg/L, trough <2 mg/L.
Other nephrotoxins:
| Drug | Mechanism |
|---|---|
| NSAIDs | Inhibit prostaglandins → reduced renal blood flow → acute interstitial nephritis, papillary necrosis |
| Contrast media (iodinated) | Direct tubular toxicity, vasoconstriction; prevent with hydration and N-acetylcysteine |
| Amphotericin B | Dose-dependent tubular toxicity; liposomal form less nephrotoxic |
| Cyclosporine, tacrolimus | Vasoactive effects on afferent arteriole; chronic interstitial fibrosis |
| Methotrexate (high dose) | Precipitation in renal tubules; requires hydration and leucovorin rescue |
| Lithium | Interferes with ADH action → nephrogenic diabetes insipidus; chronic interstitial fibrosis |
| Proton pump inhibitors | Acute interstitial nephritis (immunological) |
Haematological ADRs
| ADR | Drug(s) | Mechanism |
|---|---|---|
| Agranulocytosis | Clozapine, carbimazole, procainamide, sulphasalazine | Immune-mediated bone marrow toxicity |
| Aplastic anaemia | Chloramphenicol, phenylbutazone, sulfonamides | Direct bone marrow suppression |
| Haemolytic anaemia | Methyldopa, penicillin, sulfonamides | Autoimmune (IgG) or drug-induced ( oxidative haemolysis in G6PD) |
| Thrombocytopenia | Heparin (HIT Type II), linezolid | Immune-mediated platelet destruction |
| Bleeding tendency | Warfarin, heparin, direct oral anticoagulants, NSAIDs, aspirin | Impaired clot formation/platelet function |
| Methaemoglobinaemia | Dapsone, local anaesthetics (prilocaine), nitrates | Oxidative haemoglobin denaturation |
Heparin-induced thrombocytopenia (HIT) — important clinical distinction: Paradoxically, heparin can cause thrombosis (not bleeding) through an immune mechanism. HIT Type II is an antibody-mediated reaction where platelet factor 4 (PF4)-heparin complexes activate platelets → hypercoagulable state → venous/arterial thrombosis. HIT should be suspected when platelet count falls >50% or to <150,000/μL after 5–10 days of heparin therapy. Immediate heparin cessation and alternative anticoagulation (argatroban, bivalirudin, fondaparinux) are required. In South Africa, HIT is particularly relevant in patients receiving heparin for DVT prophylaxis post-surgery or in cardiac catheterisation labs.
Dermatological ADRs
| Reaction | Characteristics | Causative Drugs |
|---|---|---|
| Maculopapular rash | Exanthematous; immune-mediated | Ampicillin (especially in viral infection), amoxicillin |
| Urticaria/angioedema | IgE-mediated; itchy wheals | Penicillins, cephalosporins, ACE inhibitors |
| Fixed drug eruption | Same site on re-exposure; hyperpigmented | Tetracyclines, phenolphthalein, co-trimoxazole |
| SJS/TEN | Mucocutaneous blistering; ± ocular involvement | Sulphonamides, anticonvulsants, allopurinol, NSAIDs |
| DRESS | Fever, rash, eosinophilia, organ involvement | Aromatic anticonvulsants, allopurinol, sulfonamides |
| Photosensitivity | Enhanced sunburn | Tetracyclines (especially doxycycline), fluoroquinolones, thiazides |
| Exfoliative dermatitis | Erythroderma;全身红斑鳞屑性皮炎 | Gold, penicillamine, sulfasalazine, anticonvulsants |
Other Notable ADRs
ACE inhibitor-induced angioedema: Due to accumulation of bradykinin (ACE degrades bradykinin). More common in African patients (2–4× higher incidence). Can be life-threatening if laryngeal. Treatment: Fresh frozen plasma (contains kininase II), icatibant (bradykinin B2 receptor antagonist), adrenaline for anaphylaxis. Patients with history of ACE inhibitor angioedema should not be rechallenged; ARBs should be used with caution (cross-reactivity ~10%).
Statin-induced myopathy: Range: myalgia → myositis → rhabdomyolysis. Mechanism: statin accumulation in muscle cells → mitochondrial dysfunction → muscle cell necrosis. Risk increased by CYP3A4 inhibitors (macrolides, azoles), gemfibrozil (impairs statin glucuronidation), renal impairment, hypothyroidism. Monitoring: CK levels; patient-reported muscle pain. Drugs: simvastatin highest risk; pravastatin and rosuvastatin lower risk.
Diuretic-induced electrolyte disturbances:
| Diuretic | Electrolyte Effect | Clinical Consequence |
|---|---|---|
| Thiazides | ↓K⁺, ↓Mg²⁺, ↓Na⁺, hyperuricaemia, hyperglycaemia | Hypokalaemia, arrhythmias, gout |
| Loop diuretics | ↓K⁺, ↓Ca²⁺, ↓Mg²⁺, ↓Na⁺ | Hypokalaemia, ototoxicity (with aminoglycosides) |
| K⁺-sparing | ↑K⁺, ↓Na⁺ | Hyperkalaemia (especially with ACE-I/ARB or K⁺ supplements) |
Pharmacovigilance Systems
Definition and Purpose
Pharmacovigilance (PV) is the science and activities relating to:
- Detection of adverse drug reactions and other drug-related problems
- Assessment of causality, severity, and preventability
- Understanding of mechanisms
- Prevention of ADRs through informed prescribing/dispensing
- Communication and regulatory action
International Context
The WHO Programme for International Drug Monitoring, managed by the Uppsala Monitoring Centre (UMC) in Sweden, coordinates a global pharmacovigilance network. Over 150 countries participate, submitting ADR reports to VigiBase — the WHO global database of individual case safety reports (ICSRs).
South African Pharmacovigilance System
Regulatory framework:
- Medicines and Related Substances Control Act 101 of 1965 (as amended)
- SAHPRA (South African Health Products Regulatory Authority) is the national medicines regulatory authority
- The National Pharmacovigilance Programme is coordinated by SAHPRA
Key pharmacovigilance activities in South Africa:
- Spontaneous ADR reporting — healthcare professionals (doctors, pharmacists, nurses) report suspected ADRs to SAHPRA using the Yellow Card system (blue forms in South Africa)
- Active surveillance — especially for antiretroviral medicines (part of the SA HIV ART programme), TB medicines, and vaccines in the EPI (Expanded Programme on Immunisation)
- Post-marketing surveillance — phase IV studies, observational studies
- Medication safety — error reporting, near-miss reporting
The SAHPRA Yellow Card reporting system: Reports can be submitted:
- Online: www.sahpra.org.za (Yellow Card / MedSaf)
- Email: adr@sahpra.org.za
- Telephone: 0800 204 982 (toll-free)
- Post: SAHPRA, Private Bag X4008, Pretoria, 0001
Who should report: All healthcare professionals are encouraged to report suspected ADRs. Pharmacists have a professional obligation under the SAPC Good Pharmacy Practice rules to report ADRs.
Types of Pharmacovigilance Studies
| Study Type | Description | Example |
|---|---|---|
| Spontaneous reporting | Passive surveillance; healthcare professionals report suspected ADRs | Yellow Card reports to SAHPRA |
| Cohort studies | Follow groups exposed/unexposed to drug over time | Post-marketing surveillance of new ARV |
| Case-control studies | Compare cases (with ADR) to controls (without) | Association between rofecoxib and CV events |
| Cross-sectional studies | Snapshot of drug use and ADR at one time point | National adverse event surveys |
| Clinical trials | Pre-market safety data (Phase I–III) | Registration trials for new antihypertensive |
| Registries | Ongoing systematic collection of data on specific conditions | Cancer registry, ART registry |
Causality Assessment
When a suspected ADR is reported, causality assessment determines the likelihood of a causal relationship. Several scales exist:
WHO-UMC Causality Assessment Scale:
| Causality Term | Definition |
|---|---|
| Certain | Event or laboratory test abnormality, with plausible time relationship, that cannot be explained by other drugs or diseases |
| Probable/Likely | Event with reasonable time relationship, unlikely due to other drugs or disease, and follows a clinical response to withdrawal |
| Possible | Event with time relationship that could also be explained by other drugs or diseases |
| Unlikely | Event with improbable time relationship or which could be explained by other drugs or disease |
| Not assessable | Insufficient evidence to make a judgement |
Naranjo Algorithm: A structured decision tree approach giving a score that classifies the ADR as definite, probable, possible, or doubtful.
Hartwig Scale: Assesses severity and preventability of ADRs (mild, moderate, severe, life-threatening).
Medication Errors vs ADRs
A medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm. ADRs differ from medication errors:
| Aspect | ADR | Medication Error |
|---|---|---|
| Intentional | Unintended | May or may not be intentional |
| Predictability | Type A = predictable; Type B = not predictable | Preventable if proper procedures followed |
| Dose-relationship | Type A = dose-dependent | Can occur at any dose |
| Causality | Direct result of drug’s pharmacology or immune response | Result of human/ system failure |
Preventable ADRs: Those resulting from medication errors are considered preventable. Studies suggest 30–70% of ADRs may be preventable with appropriate systems and procedures.
Medication Safety
The Four Stages of Medication Use
ADRs can occur at any of the four stages of medication use:
- Prescribing — inappropriate drug selection, dose, or duration; allergy conflicts; interaction risks
- Dispensing — incorrect drug, incorrect dose, incorrect labelling, poor counselling
- Administration — wrong route, wrong time, wrong patient, wrong dose (the “5 rights”)
- Monitoring — failure to monitor for therapeutic response and ADRs
High-Risk Patients
| Patient Group | Specific Risks |
|---|---|
| Elderly | Altered pharmacokinetics; polypharmacy; multiple comorbidities; cognitive impairment |
| Paediatric | Immature organ function; weight-based dosing errors; formulation issues |
| Renal impairment | Accumulation of renally cleared drugs; dose adjustment required |
| Hepatic impairment | Reduced metabolism; altered protein binding; risk of hepatic failure |
| Pregnant/breastfeeding | Foetal/infant exposure; drug selection carefully considered |
| HIV/AIDS | Immune compromise; ARV-drug interactions; Ols (opportunistic infections) |
| Critical care patients | Multiple IV drugs; pump programming errors; rapid changes in pharmacokinetics |
Strategies for ADR Prevention
Prescribing stage:
- Allergy checking before prescribing
- Review of current medication list for interactions
- Dose adjustment for organ dysfunction
- Consideration of pharmacogenetic factors
- Use of formulary/restricted drugs where appropriate
Dispensing stage:
- Check for drug interactions and allergies (computerised or manual)
- Accurate labelling with drug name, dose, instructions
- counselling on expected effects and warning signs
- Quality assurance: double-check for high-risk drugs
Administration stage:
- 5 (or 6) rights of medication administration
- Barcode scanning at bedside (where available)
- Patient identification before administration
Monitoring stage:
- Therapeutic drug monitoring for narrow TI drugs
- Routine observations (BP, HR, temperature)
- Patient education on what to report
Special Considerations in South African Pharmacy Practice
ART and ADR Monitoring
South Africa’s large ART programme (over 5 million patients on treatment) creates specific pharmacovigilance challenges:
Common ART ADRs:
| ARV | Common ADRs | Monitoring |
|---|---|---|
| Efavirenz | CNS effects (vivid dreams, dizziness); hepatotoxicity; rash; teratogenicity | CNS symptoms (usually transient); LFTs |
| Tenofovir (TDF) | Renal toxicity; bone density reduction | eGFR; phosphate; bone density monitoring |
| Nevirapine | Hepatotoxicity; severe rash (SJS) | LFTs (especially first 18 weeks); skin monitoring |
| Kaletra (LPV/r) | GI intolerance; metabolic effects (hyperglycaemia, hyperlipidaemia) | Fasting glucose/lipids |
| Zidovudine (AZT) | Anaemia; neutropenia; myopathy | FBC (especially in first 3 months) |
SAHPRA and the ART programme: All serious and unexpected ADRs with ARVs must be reported to SAHPRA. The Pharmacovigilance Centre for ART (PVC-ART) operates within SAHPRA to coordinate ART-specific PV activities.
Traditional Medicine and ADRs
In South Africa, traditional medicine use is widespread. Specific considerations:
- Traditional medicines are not subject to SAHPRA regulation for quality, safety, and efficacy
- ADR reports involving traditional medicines should still be reported to SAHPRA
- Traditional medicines may cause ADRs directly, or may interact with conventional medicines (see pharma-008)
- Contamination of traditional medicines with undeclared conventional drugs (e.g., corticosteroids, NSAIDs, benzodiazepines) has been documented
- Heavy metal contamination (lead, mercury, arsenic) is a documented risk
ADR Reporting Obligations
Professional obligations:
- SAPC Good Pharmacy Practice (GPP) rules require pharmacists to have systems for detecting and reporting ADRs
- ADR reporting is a professional and ethical obligation, not merely a suggestion
- Failure to report known ADRs may constitute professional misconduct
What to report:
- All suspected ADRs, including those that are mild or expected
- All serious ADRs (life-threatening, causing hospitalisation, significant disability, or death)
- All unexpected ADRs (not described in the approved package insert)
- All ADRs in children
- All ADRs with traditional medicines, complementary medicines, and supplements
SAPC Examination Focus Areas
The SAPC examination frequently tests ADR knowledge through case scenarios and multiple-choice questions.
High-yield topics for the SAPC exam:
- ADR classification (Type A–F) — be able to classify a given ADR and identify management approach
- Paracetamol overdose and NAC — mechanism of toxicity, antidote, treatment window (8 hours)
- SJS/TEN — causative drugs common in SA (co-trimoxazole), management (ICU/burn unit)
- HIT (heparin-induced thrombocytopenia) — paradoxical thrombosis, immediate heparin cessation
- ACE inhibitor angioedema — bradykinin mechanism, higher incidence in African patients, management
- Statin myopathy — spectrum from myalgia to rhabdomyolysis, CYP3A4 interactions, CK monitoring
- Drug-induced QT prolongation and torsades — drugs causing it, risk factors, management
- Pharmacovigilance reporting — how and what to report in South Africa, SAHPRA Yellow Card system
- Drug-induced pulmonary fibrosis — amiodarone, nitrofurantoin
- Clozapine agranulocytosis — mandatory ANC monitoring (weekly × 18 weeks, then monthly)
- Drug-induced liver injury patterns — hepatocellular vs cholestatic vs mixed
- Paediatric ADRs — different pharmacokinetics, age-specific toxicities
Summary of Key Concepts
- ADRs are classified as Type A (predictable, common) through Type F (therapeutic failure)
- Type B (idiosyncratic) reactions are unpredictable and can be severe
- Immunological mechanisms follow the four Gell and Coombs hypersensitivity types
- Pharmacovigilance is the systematic monitoring of medicine safety
- South Africa’s pharmacovigilance system is coordinated by SAHPRA; the Yellow Card system allows reporting by all healthcare professionals
- Medication errors that cause ADRs are considered preventable
- High-risk populations include the elderly, children, renally/hepatically impaired patients, pregnant women, and HIV/AIDS patients
- Pharmacists have a professional obligation to detect, report, and help manage ADRs
- In South Africa, ART ADR monitoring and traditional medicine safety are priority areas