Is a new substance safe for a patient with hATTR amyloidosis?

Safety of New Substances in hATTR Amyloidosis

Your question lacks specificity about which substance you're asking about, but I can provide a comprehensive framework for evaluating medication safety in patients with hATTR amyloidosis based on the most critical contraindications and precautions.

Medications to ABSOLUTELY AVOID

Digoxin and calcium channel blockers are strictly contraindicated in all patients with cardiac amyloidosis, regardless of whether they have hATTR or other forms. 1, 2

• Digoxin binds to amyloid fibrils and causes toxicity even at normal serum levels 2
• Calcium channel antagonists bind to amyloid fibrils and cause exaggerated hypotensive responses 2
• These medications can precipitate life-threatening complications and should never be initiated 1

Critical Medication Considerations by Clinical Context

If the Patient Has Heart Failure

Sympathomimetic agents (midodrine, droxidopa) and volume-expanding agents (salt tablets, fludrocortisone) may be poorly tolerated due to restrictive cardiac physiology. 1, 3

• Midodrine can cause supine hypertension, fluid retention, scalp itching, and urinary retention 1, 3
• Fludrocortisone causes supine hypertension, hypokalemia, and edema 1
• If orthostatic hypotension requires midodrine or droxidopa that cannot be weaned, this constitutes a contraindication to heart transplantation 1, 3

If the Patient Has Neuropathic Pain

Tricyclic antidepressants (amitriptyline, nortriptyline) should be used with extreme caution due to multiple cardiac risks. 1

• Risk of serotonin syndrome 1
• Caution specifically required if cardiac disease or dysrhythmia history present 1
• Can worsen orthostatic hypotension and autonomic symptoms 4
• Cause sedation, dry mouth, confusion, weight gain, urinary retention, constipation, and blurred vision 1

Duloxetine carries bleeding risk and requires caution with anticoagulants. 1

• Risk of serotonin syndrome 1
• Increased bleeding risk particularly important if patient on anticoagulants 1
• Withdrawal syndromes with abrupt discontinuation 1
• Caution with hepatic failure 1

If the Patient Has Renal Insufficiency

Pregabalin and gabapentin both require dose adjustment in kidney insufficiency. 1

• Pregabalin: additional concern with psychiatric disease or addiction history due to euphoria risk (Schedule V controlled substance) 1
• Both cause sedation, dizziness, confusion, edema, and weight gain 1

Disease-Modifying Therapies: Special Monitoring Requirements

If Considering TTR Silencers

All TTR silencers (patisiran, inotersen, vutrisiran) are ONLY approved for ATTRv polyneuropathy, NOT for ATTRwt amyloidosis or cardiac-only disease. 1, 4

Patisiran requires premedication to prevent infusion reactions: 1, 5

• Dexamethasone 10 mg IV 1
• Acetaminophen 500 mg 1
• Diphenhydramine 50 mg 1
• Famotidine 20 mg 1
• All patients require vitamin A supplementation 3,000 IU daily 1, 4, 5

Inotersen requires intensive monitoring due to serious toxicity risks: 1

• Check platelet count weekly 1
• Check serum creatinine, eGFR, and UPCR every 2 weeks 1
• Risk of thrombocytopenia and glomerulonephritis 1, 4
• Requires vitamin A supplementation 3,000 IU daily 1, 4

Vutrisiran has the simplest monitoring but still requires vitamin A: 1, 6

• Requires vitamin A supplementation 3,000 IU daily 1, 4
• Subcutaneous administration every 3 months 1, 6

Post-Liver Transplant Patients

TTR gene silencing therapy can be used post-liver transplant but requires vigilant monitoring for complications. 7, 8

• Risk of transplant rejection, particularly with inadequate immunosuppression 7
• Frequent monitoring of renal, liver, and bone marrow functions necessary 8
• Thrombocytopenia is a common reason for discontinuation 8
• Patients who discontinue treatment may experience worsening neuropathy 8

Cardiovascular Medications: General Principles

β-blockers and atrioventricular nodal agents should be used with caution due to low stroke volume in restrictive cardiomyopathy. 2

Renin-angiotensin system inhibitors and vasodilators should be deprescribed if orthostatic hypotension develops. 2

Sodium-glucose cotransporter 2 inhibitors should be considered regardless of ejection fraction. 2

Common Pitfalls to Avoid

• Never assume a medication safe for heart failure is safe for cardiac amyloidosis - the restrictive physiology creates unique contraindications 1, 2
• Never use TTR silencers for ATTRwt disease - they are only proven effective for ATTRv polyneuropathy 1, 4
• Never forget vitamin A supplementation with any TTR silencer - all three agents reduce vitamin A levels 1, 4, 5
• Never initiate inotersen without establishing weekly platelet monitoring and biweekly renal function monitoring 1