What is the management of recurrent orthostatic hypotension despite midodrine (Midodrine) 50mg and fludrocortisone (Fludrocortisone) in a patient with tuberculosis septic joint treated with RIPE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) regimen and prolonged QT interval on electrocardiogram (ECG)?

From the Guidelines

For recurrent orthostatic hypotension despite midodrine and fludrocortisone in a patient with tuberculosis septic joint on RIPE therapy and prolonged QTc, I recommend temporarily discontinuing midodrine and reducing fludrocortisone to 0.05mg daily while implementing non-pharmacological measures. These measures include gradual position changes, increased fluid intake (2-3L daily), increased salt intake (8-10g daily), compression stockings, and elevating the head of the bed 4-6 inches, as suggested by the most recent guidelines on orthostatic hypotension management 1. The RIPE regimen (rifampin, isoniazid, pyrazinamide, ethambutol) likely contributes to both the orthostatic hypotension and QTc prolongation, particularly rifampin through enzyme induction affecting midodrine metabolism and isoniazid potentially affecting cardiac conduction. Once the QTc normalizes, consider reintroducing midodrine at a lower dose (2.5mg three times daily) with careful monitoring, or alternatively, droxidopa 100mg three times daily could be considered as it may have less impact on QTc, based on the FDA approval for the treatment of orthostatic hypotension 1. Regular ECG monitoring is essential during treatment, and electrolyte abnormalities (particularly potassium, magnesium, and calcium) should be corrected as they can worsen QTc prolongation, as noted in the management of patients with drug-resistant tuberculosis 1. Key considerations in managing this patient include:

• Monitoring for QTc prolongation and its associated risks, as highlighted in the DELIBERATE trial 1
• Adjusting medications to minimize the risk of further QTc prolongation
• Implementing non-pharmacological measures to manage orthostatic hypotension, as recommended in the standards of care for diabetes-2024 1
• Ensuring adequate fluid and salt intake to help manage orthostatic hypotension, as suggested by the guidelines on orthostatic hypotension management 1.

From the FDA Drug Label

The patient should be cautioned to report symptoms of supine hypertension immediately. Midodrine should be used with caution in orthostatic hypotensive patients who are also diabetic, as well as those with a history of visual problems who are also taking fludrocortisone acetate, which is known to cause an increase in intraocular pressure and glaucoma. Midodrine use has not been studied in patients with renal impairment Because desglymidodrine is eliminated via the kidneys, and higher blood levels would be expected in such patients, midodrine should be used with caution in patients with renal impairment, with a starting dose of 2. 5 mg Midodrine use has not been studied in patients with hepatic impairment. Midodrine should be used with caution in patients with hepatic impairment, as the liver has a role in the metabolism of midodrine When administered concomitantly with midodrine hydrochloride tablets, cardiac glycosides may enhance or precipitate bradycardia, A. V. block or arrhythmia. The risk of hypertension increases with concomitant administration of drugs that increase blood pressure

The management of recurrent orthostatic hypotension despite midodrine (Midodrine) 50mg and fludrocortisone (Fludrocortisone) is not directly addressed in the provided drug label. Key considerations for the patient include:

• Monitoring blood pressure
• Evaluating renal and hepatic function
• Avoiding concomitant use of drugs that increase blood pressure
• Careful monitoring of supine hypertension in patients taking salt-retaining steroid therapy However, no specific guidance is provided for managing recurrent orthostatic hypotension in this context 2.

From the Research

Management of Recurrent Orthostatic Hypotension

The management of recurrent orthostatic hypotension despite midodrine and fludrocortisone in a patient with tuberculosis septic joint treated with RIPE regimen and prolonged QT interval on electrocardiogram (ECG) is complex and requires careful consideration of the underlying pathophysiology and potential interactions between medications.

Pharmacologic Treatment Options

• Midodrine is an effective therapeutic option for the management of orthostatic hypotension, as it increases 1-minute standing systolic blood pressure and improves standing time and energy level 3.
• Fludrocortisone is also used to treat orthostatic hypotension, and its combination with midodrine may be beneficial in some patients 4, 5.
• However, the use of midodrine and fludrocortisone may not be sufficient to control orthostatic hypotension in all patients, and other treatment options may need to be considered.

Potential Interactions and Complications

• Midodrine can cause urologic adverse effects, such as urinary retention and hydroureteronephrosis, particularly in patients with spinal cord injury 6.
• The RIPE regimen, which includes rifampicin, isoniazid, pyrazinamide, and ethambutol, may interact with other medications and exacerbate orthostatic hypotension.
• Prolonged QT interval on ECG may be a concern when using certain medications, and careful monitoring of the patient's cardiac status is necessary.

Individualized Treatment Approach

• The treatment of orthostatic hypotension should be individualized, taking into account the patient's underlying medical conditions, medications, and response to treatment 4.
• A comprehensive approach to management, including nonpharmacologic and pharmacologic interventions, is necessary to control orthostatic hypotension and prevent complications.