What are the renal contraindications and dosing recommendations for Cafergot (ergotamine tartrate + caffeine) in patients with reduced eGFR?

Cafergot Renal Contraindications

Cafergot (ergotamine tartrate + caffeine) should be used with extreme caution in patients with renal failure and is relatively contraindicated in this population due to risk of ergot toxicity and vasospastic ischemia. 1, 2

Specific Renal Contraindications

Dihydroergotamine (DHE), a related ergot derivative, explicitly lists renal impairment as a contraindication. 1 While the evidence provided does not specify an exact eGFR cutoff for Cafergot itself, the guideline data for DHE suggests that ergot alkaloids as a class should be avoided in patients with compromised renal function.

Key Contraindications for Ergot Derivatives:

• Renal impairment is listed as a contraindication for dihydroergotamine 1
• Renal failure is specifically mentioned as requiring extreme caution with Cafergot 2
• Patients with peripheral vascular disease should avoid Cafergot due to vasoconstrictive effects 2

Mechanism of Concern in Renal Impairment

Ergotamine causes vasoconstriction through alpha-adrenergic agonism and interactions with prostaglandins, calcium, and serotonin, affecting both arteries and veins. 2 In patients with renal impairment:

• Reduced drug clearance leads to accumulation and increased risk of ergot toxicity 3
• Elimination occurs primarily through hepatic metabolism and biliary excretion, but renal dysfunction can still impair overall clearance 3
• Vasoconstrictive effects may be exacerbated in patients with compromised renal perfusion 2

Clinical Manifestations of Ergot Toxicity

Iatrogenic ergotism can progress to fulminant necrosis and gangrene, presenting with peripheral vascular insufficiency symptoms. 2 Early warning signs include:

• Headache, nausea, vomiting, and general malaise 4
• Coldness and paresthesias of extremities 3
• Muscle pains and weakness 3
• Arterial spasm with typical angiographic patterns 2

Dosing Limitations (When Use Cannot Be Avoided)

Maximum dosing must be strictly limited to prevent toxicity: no more than 6 tablets per attack, 10 tablets per week, or 10mg ergotamine per week. 1, 3 Standard dosing for Cafergot:

• Initial dose: 2 tablets (100mg caffeine/1mg ergotamine each) at onset 1
• Subsequent doses: 1 tablet every 30 minutes 1
• Maximum per attack: 6 tablets 1
• Maximum per week: 10 tablets 1

Safer Alternatives for Migraine in Renal Impairment

Triptans are preferred over ergot derivatives for most patients and do not carry the same renal contraindications. 1 Specific options include:

• Sumatriptan: Available in subcutaneous, intranasal, and oral forms; no renal dose adjustment required 1
• Naratriptan: Longest half-life among triptans, may reduce recurrence 1
• Rizatriptan: Available as absorbable wafer (Maxalt MLT) for patients with nausea 1

Critical Monitoring and Management

If ergotamine toxicity occurs, immediate discontinuation is mandatory along with cessation of cigarette smoking and caffeine. 2 Treatment approach:

• Mild cases: Discontinuation alone may suffice 2
• Acute severe insufficiency: Nitroprusside is the drug of choice 2
• Less urgent situations: Prazosin has been effective 2
• Mechanical intervention: Intra-arterial balloon dilatation may be helpful 2

Common Pitfalls to Avoid

• Do not use Cafergot in combination with triptans - this is an absolute contraindication due to additive vasoconstrictive effects 1
• Do not exceed weekly dosing limits - ergotamine dependence and rebound headaches are common with overuse 3, 4
• Do not ignore early toxic symptoms - headache, nausea, and malaise may indicate impending serious toxicity 4
• Do not use in patients already on beta blockers, antihypertensives, or SSRIs when considering DHE, as interactions increase risk 1