What are the reasons to hold a medication?

Reasons to Hold Medications

Medications should be held when there is evidence of intolerable side effects, acute illness causing volume depletion, laboratory abnormalities indicating drug accumulation or toxicity, or when the risk of continuing therapy outweighs potential benefits.

Clinical Scenarios Requiring Medication Hold

Acute Illness with Volume Depletion ("Sick Day" Situations)

Hold the following medication classes during acute dehydrating illnesses (vomiting, diarrhea, fever, reduced oral intake):

• SGLT2 inhibitors - should be withheld during any acute illness with volume depletion 1
• Metformin - hold during acute illness to prevent lactic acidosis risk 1, 2
• ACE inhibitors/ARBs and ARNIs - withhold during volume depletion to prevent acute kidney injury 1
• Diuretics (loop, thiazide, potassium-sparing) - hold to avoid worsening dehydration 1
• NSAIDs - discontinue during acute illness due to renal perfusion effects 1
• Direct renin inhibitors - withhold during volume depletion 1

Specific triggers for holding these medications include: signs of volume depletion (reduced level of consciousness, severe vomiting, low blood pressure, tachycardia, fever), with resumption only after 24-48 hours of symptom resolution and return to normal eating/drinking 1

Metformin-Specific Hold Criteria

Hold metformin immediately in the following situations:

• eGFR <30 mL/min/1.73 m² - absolute contraindication 2
• Before contrast imaging - stop at time of or prior to iodinated contrast procedures in patients with eGFR 30-60 mL/min/1.73 m², history of liver disease, alcoholism, heart failure, or intra-arterial contrast administration; restart only after 48 hours if renal function stable 2
• Surgical procedures - temporarily discontinue when food/fluid intake restricted 2
• Hypoxic states - discontinue with acute heart failure, cardiovascular collapse, shock, acute MI, sepsis, or conditions with hypoxemia 2
• Suspected lactic acidosis - discontinue immediately and arrange prompt hemodialysis 2
• Hepatic impairment - avoid use with clinical or laboratory evidence of liver disease 2

Warfarin Hold Criteria

Warfarin must be held for:

• Planned surgery involving CNS, eye, or procedures creating large open surfaces 3
• Active bleeding from GI, GU, or respiratory tracts 3
• Cerebrovascular hemorrhage or dissecting aortic aneurysm 3
• Spinal puncture or diagnostic/therapeutic procedures with uncontrollable bleeding potential 3
• Major regional or lumbar block anesthesia 3
• Bacterial endocarditis or pericarditis with effusion 3

More frequent INR monitoring is required when initiating or discontinuing interacting medications or botanicals, as numerous drugs can unpredictably increase or decrease warfarin effects 3

IL-2 Therapy Hold Criteria

Hold IL-2 doses when:

• Urine output falls below 4 mL/kg over 8 hours 1
• Platelets drop below 50,000 x10⁹/L 1
• ≥3 relative toxicity criteria are present (specific vital sign changes, organ dysfunction) 1
• One dose held - can resume next scheduled dose with extreme caution if recovered 1
• Two consecutive doses held - permanently discontinue IL-2 1

Intolerable Side Effects

Discontinue medications when side effects make continued use untenable:

• Significant weight gain affecting quality of life 1
• Growth concerns in pediatric patients 1
• Development of involuntary movements (e.g., tardive dyskinesia from antipsychotics) 1
• Severe allergic reactions - discontinue immediately and avoid structurally related drugs due to cross-reactivity risk 4, 5
• Drug-induced anaphylaxis - absolute contraindication to future use; injectable epinephrine is treatment of choice 5

Immunosuppressive Medication Adjustments

Hold or adjust immunosuppressive agents around vaccination:

• Methotrexate - withhold for 2 weeks before and after vaccination (but not >2 weeks to prevent disease flare) 1
• JAK inhibitors - hold for 1-2 weeks on either side of vaccination when used with methotrexate 1
• Anti-CD20 agents (rituximab) - administer with minimum 4-week gap before and 6-month gap after vaccination 1
• High-dose corticosteroids (>10 mg prednisone daily equivalent) - consider tapering around vaccination time 1

Medication No Longer Warranted or Effective

Consider discontinuation when:

• Patient has recovered and may no longer need the medication 1
• Current prescriber determines medication is not warranted after reviewing previous psychiatric symptoms and medication response history 1
• Medication considered no longer effective - requires thorough history review to ensure discontinuation won't cause unexpected symptom return 1

Critical caveat: Develop a specific monitoring plan before discontinuation, as symptom return may occur hours to months after the last dose depending on the condition (ADHD symptoms may return in hours-days, while mood/anxiety symptoms may take weeks-months) 1

Polypharmacy and Deprescribing Considerations

Hold medications as part of deprescribing efforts when:

• Potentially inappropriate medications (PIMs) are identified using validated tools (Beers criteria, STOPP/START) 1
• Risk of adverse drug reactions outweighs benefits in elderly patients with multimorbidity 1
• Drug underuse is present - paradoxically, some essential cardiovascular medications are inappropriately withheld due to fear of side effects, requiring reassessment 1

Important distinction: Certain cardiovascular drugs (beta-blockers, clonidine, digoxin, antiplatelets, statins) require careful planning when discontinuing due to potential adverse withdrawal effects 1

Medications That Do NOT Require Tapering

The following can be stopped abruptly without physiological withdrawal:

• Methylphenidate - short half-life (~2 hours) with rapid clearance; side effects reversible with discontinuation; no dangerous withdrawal syndrome 6
• Atomoxetine - no tapering required, though monitor for symptom return over weeks to months 7

Contrast with medications requiring mandatory taper:

• Extended-release guanfacine and clonidine - must always be tapered due to rebound hypertension risk 7
• Benzodiazepines and SSRIs - require gradual taper to avoid withdrawal symptoms or rebound worsening 1

Common Pitfalls to Avoid

• Failing to obtain collateral history before discontinuing psychiatric medications - patients/families may not accurately describe previous symptoms, leading to unexpected symptom return 1
• Discontinuing medications in short-stay inpatient settings without adequate outpatient monitoring arrangements - may result in unmonitored symptom return after discharge 1
• Not monitoring for return of underlying symptoms after stopping medications like stimulants or atomoxetine - ADHD symptoms may re-emerge once drug effect wears off 6, 7
• Confusing drug allergy with intolerance or side effects - true IgE-mediated allergic reactions are absolute contraindications and may cross-react with related drugs, while intolerances and side effects may be manageable or non-reproducible 4, 5, 8