What is the appropriate dosing of primidone for an adult or elderly patient with chronic obstructive pulmonary disease (COPD) under hospice care, presenting with tremors?

Primidone Dosing for Tremors in COPD Hospice Patients

For an adult or elderly patient with COPD under hospice care presenting with tremors, initiate primidone at 50 mg at bedtime for the first 3 days, then gradually titrate upward over 10 days to a maintenance dose of 250 mg three times daily, with careful monitoring for sedation and respiratory depression given the significant risks in this vulnerable population. 1

Initial Dosing Protocol

The FDA-approved initiation schedule for primidone in adults should be followed, but with heightened caution in COPD patients under hospice care 1:

• Days 1-3: 50 mg at bedtime (use the 50 mg tablet, not the standard 100-125 mg starting dose)
• Days 4-6: 50 mg twice daily
• Days 7-9: 100 mg twice daily
• Day 10 onward: 125-250 mg three times daily as maintenance 1

Critical Considerations for COPD Hospice Patients

Respiratory depression risk is substantially elevated in this population. Benzodiazepines and sedating medications should be used at lower doses in patients with COPD, and primidone—which is metabolized to phenobarbital—carries similar risks 2. The ESMO guidelines specifically recommend using lower doses of sedating medications in patients with COPD or when co-administered with other central nervous system depressants 2.

Start even lower than standard dosing if possible. While the FDA label suggests 100-125 mg as the initial dose for most adults, elderly patients and those with significant comorbidities like COPD benefit from starting at 50 mg 1. Recent evidence suggests that very low initial dosing (as low as 2.5 mg in suspension form) has been studied, though this did not improve tolerability compared to 25 mg tablets 3.

Maintenance Dosing and Titration

The usual maintenance dose is 250 mg three to four times daily (750-1000 mg/day total). 1 However, in elderly hospice patients with COPD, the lower end of this range (250 mg three times daily = 750 mg/day) is more appropriate initially. The FDA label notes that doses can be increased to 500 mg four times daily (2000 mg/day maximum) if needed, but this should be approached with extreme caution in this population 1.

Therapeutic serum levels range from 5-12 mcg/mL. 1 Monitoring serum levels may be helpful for optimal dosage adjustment, particularly in patients with unpredictable responses or concerning side effects 1.

Efficacy Expectations

Primidone improves tremor in approximately 50% of patients with essential tremor. 4 It is considered a first-line agent alongside propranolol, and if monotherapy is inadequate, the two can be combined 4. However, in the hospice setting where goals focus on comfort rather than complete tremor suppression, partial improvement may be sufficient.

Common Pitfalls and Safety Concerns

Acute intolerance occurs in up to 82% of patients after the first dose, manifesting as somnolence, ataxia, confusion, dizziness, and nausea 5. This risk can be reduced to 17% by pre-treating with low-dose phenobarbital (10 mg/day for 2-3 weeks), though this approach adds complexity that may not align with hospice goals 5.

One-third of patients fail to tolerate primidone due to early side effects. 3 In the hospice context, where quality of life is paramount, discontinuation should be considered promptly if side effects are distressing rather than pushing through a prolonged titration 3.

Falls risk is significantly increased with sedating medications in elderly patients, and this is compounded when primidone is combined with other medications common in hospice care 6. The American Geriatrics Society recommends careful assessment of fall risk, medication review, and patient education about dizziness and somnolence 6.

Avoid combining with benzodiazepines when possible due to the risk of oversedation and respiratory depression, which is particularly dangerous in COPD patients 2. If benzodiazepines are necessary for anxiety or agitation in hospice care, use the lowest effective doses (e.g., lorazepam 0.25-0.5 mg or midazolam 0.5-1 mg) 2.

Alternative Considerations

If primidone is poorly tolerated or contraindicated, propranolol is the other first-line option for essential tremor 4. However, propranolol should be used cautiously in COPD, as asthma is a contraindication (though COPD itself is not an absolute contraindication per ESC guidelines) 2. Beta-blockers can cause bronchospasm in some COPD patients, so careful monitoring is required 2.

Gabapentin or topiramate may be considered as second-line agents if primidone and propranolol fail or are not tolerated 4. Gabapentin carries its own fall risk in elderly patients and requires dose adjustment in renal impairment 6.