What is the management of recurrent orthostatic hypotension despite midodrine and fludrocortisone (Florinef) in a patient with a septic joint due to tuberculosis, treated with a rifampicin (Rifadin)-based regimen?

From the Guidelines

For recurrent orthostatic hypotension despite midodrine and fludrocortisone in a patient with tuberculosis septic joint on rifampin-based therapy, I recommend temporarily increasing fludrocortisone to 0.2 mg daily and midodrine to 10 mg three times daily while monitoring blood pressure. This approach is based on the understanding that rifampin induces cytochrome P450 enzymes, which can accelerate the metabolism of both midodrine and fludrocortisone, thereby reducing their effectiveness 1.

Non-Pharmacological Interventions

In addition to adjusting the doses of midodrine and fludrocortisone, several non-pharmacological measures can be beneficial:

• Compression garments, such as thigh-high stockings, can improve orthostatic symptoms and blunt associated decreases in blood pressure 1.
• Increased salt and fluid intake, aiming for 2-3 liters of fluid daily, can help improve blood pressure and reduce symptoms of orthostatic hypotension, although this should be done cautiously in patients with a history of hypertension, renal disease, heart failure, or cardiac dysfunction 1.
• Elevating the head of the bed at night can also help mitigate the effects of orthostatic hypotension.

Monitoring and Alternative Therapies

It is crucial to monitor blood pressure and electrolytes weekly during dose adjustments to avoid supine hypertension and other potential side effects. If hypotension persists despite these measures, considering alternative agents that are not affected by rifampin interactions may be necessary. Pyridostigmine, at a dose of 30-60 mg three times daily, could be an option as it improves orthostatic tolerance through increases in peripheral vascular resistance and blood pressure 1.

Long-Term Considerations

Once the tuberculosis treatment is complete, and the rifampin-based therapy is discontinued, the doses of midodrine and fludrocortisone will likely need to be reduced to prevent hypertension, as the enzyme induction effect of rifampin resolves. Continuous monitoring and adjustment of these medications, along with the non-pharmacological interventions, will be essential to manage orthostatic hypotension effectively while minimizing potential side effects.

From the Research

Management of Recurrent Orthostatic Hypotension

• The management of recurrent orthostatic hypotension despite midodrine and fludrocortisone in a patient with a septic joint due to tuberculosis, treated with a rifampicin-based regimen, involves a combination of non-pharmacological and pharmacological interventions 2.
• Non-pharmacological strategies include avoiding large carbohydrate-rich meals, limiting alcohol consumption, maintaining adequate hydration, adding salt to foods, and using compression stockings, tilt-table exercises, or abdominal binders 3.
• Pharmacological treatment options include the use of fludrocortisone, midodrine, pyridostigmine, and droxidopa, as well as pseudoephedrine, octreotide, and atomoxetine 3.
• Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure, and is considered a first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures 4.
• Midodrine is a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine, and has been shown to significantly increase 1-minute standing systolic blood pressure compared with placebo 5.

Treatment Options

• Atomoxetine has been shown to be an effective and safe agent for symptom improvement and blood pressure control in elderly patients with primary orthostatic hypotension 3.
• Midodrine has been shown to have similar efficacy to dihydroergotamine mesylate, norfenefrine, fludrocortisone, and etilefrine, and to be more effective than dimetofrine and ephedrine in patients with orthostatic hypotension 5.
• Fludrocortisone may not be harmful in the long term for familial dysautonomia, but it is unclear if this translates to long-term improvements in blood pressure drop or a meaningful improvement in orthostatic symptoms 4.

Considerations

• The risk of supine hypertension associated with midodrine therapy can be reduced by taking the final daily dose at least 4 hours before bedtime 5.
• Treatment of orthostatic hypotension must be individualized, and the goal of treatment is the improvement of the patient's functional capacity, rather than a target blood pressure 6.
• Current approaches to treating orthostatic hypotension neither reverse nor stabilize the disease process in autonomic disorders 6.