Off-Label Prescribing in Palliative Care: A Systematic Approach
Off-label prescribing is unavoidable and appropriate in palliative care when aligned with patient-centered goals of comfort and quality of life, but requires structured informed consent, documentation of evidence quality, and ongoing monitoring for adverse effects. 1, 2
Prevalence and Clinical Reality
Off-label use comprises 14.5% to 35% of all prescriptions in palliative care settings, with the majority (70%) supported by strong evidence for their intended use. 3, 4 The most frequently prescribed off-label medications include haloperidol (for delirium), chlorpromazine, dexamethasone, glycopyrrolate (for secretions), and opioids like hydromorphone and morphine for dyspnea. 3 This practice is unavoidable because regulatory approval studies are unlikely to occur for many palliative applications. 2
When Off-Label Prescribing is Appropriate
Prescribe off-label medications when standard FDA-approved therapies have failed and patients have treatment-resistant symptoms causing physical or psychological distress, particularly when the goal has shifted from longevity to comfort and quality of life. 1, 5
Key scenarios include:
- Delirium management (36% of off-label prescriptions) using antipsychotics like haloperidol 3
- Dyspnea control (20% of off-label prescriptions) using opioids 3
- Secretion management (sialorrhea, bronchorrhea) using anticholinergics 2
- Refractory symptoms including pruritus, singultus, gastroparesis, and hot flashes 2
Required Steps for Safe Off-Label Prescribing
1. Align with Patient-Centered Goals of Care
Ensure ongoing discussions about goals of care occur before initiating off-label therapy, confirming that preferences and priorities align with the treatment plan. 5 All medications prescribed should be individualized to complement patient values and preferences, particularly as care transitions from longevity-focused to comfort-focused. 5
2. Obtain Informed Consent
Document informed consent specifically for off-label use, despite the reality that only 20% of prescribers consistently obtain consent. 4 This represents a critical gap in current practice that must be addressed. 6 Patients require full information about:
- The medication's lack of regulatory approval for this specific indication 7
- Available evidence supporting its use 1
- Known adverse effect profile and monitoring plan 1
3. Evaluate Evidence Quality
Select off-label medications using FDA labeling, medical literature, published guidelines, drug compendia, and continuing education resources. 1 Prioritize medications with strong supporting evidence (which represents 70% of off-label palliative prescriptions). 3
Establish baseline and ongoing monitoring based on the medication's known adverse effect profile. 1 Evaluate drug interactions carefully before initiating therapy, particularly given that polypharmacy (≥5 medications) increases adverse drug reaction risk. 5
4. Special Population Considerations
Exercise additional caution in pediatric and elderly patients, as safety profiles may differ substantially from adult populations. 1 Elderly patients have increased vulnerability due to:
- Declining renal function requiring consideration of prolonged drug elimination 8
- Cognitive impairment affecting medication management 8
- Polypharmacy increasing toxicity risk 5
5. Documentation Requirements
Document the indication for off-label use, evidence supporting the decision, informed consent discussion, and therapy effects with particular rigor. 7 This documentation is essential because authorization studies are lacking, making systematic reporting critical for advancing the evidence base. 7
6. Implement Team-Based Approach
Optimal effectiveness requires collaboration between primary care clinicians, specialists, and palliative care teams to deliver patient-centered care. 5 A multidisciplinary approach is necessary to navigate evolving circumstances and personal goals of care, particularly for adults with multiple chronic conditions on intricate drug regimens. 5
Involve clinical pharmacists when available for medication review and interaction screening. 9
Critical Pitfalls to Avoid
Do not mistake off-label prescribing for carte blanche to add medications without evidence. The distinction must be made between situations where quality evidence exists but registration has not been updated versus situations where evidence has not been generated. 6
Avoid the "prescribing cascade" where new symptoms from medication effects are mistaken for new diseases requiring additional medications. 9 This is particularly problematic when off-label medications cause adverse effects that prompt further prescribing.
Do not assume consent is optional. Despite 97% of palliative care units lacking policies on off-label use and 20% of prescribers never obtaining consent, this represents substandard practice requiring correction. 4, 6
Current Policy Gap
Recognize that most palliative care units (up to 97%) lack formal policies or guidance on handling off-label drug use, creating legal and ethical vulnerabilities. 4 This gap necessitates individual clinician vigilance in following the structured approach outlined above until institutional policies are developed. 6