From the Guidelines
Long-term use of midodrine can cause peripheral cyanosis and paresthesia in the upper limbs due to its vasoconstrictive effects. Midodrine is a peripheral selective α1-adrenergic agonist used to treat orthostatic hypotension, and it works by causing vasoconstriction to increase blood pressure 1. This vasoconstriction can sometimes be excessive, particularly in the extremities, leading to reduced blood flow that manifests as peripheral cyanosis (bluish discoloration of the skin) and paresthesia (abnormal sensations like tingling, numbness, or pins and needles).
The potential risks of midodrine, including peripheral cyanosis and paresthesia, should be weighed against its possible benefit, particularly in patients with underlying vascular disease or those taking other medications that affect vascular tone 1. The dosing of midodrine should be individually tailored, up to two to four times 10 mg/day, with the first dose taken before arising and use avoided several hours before planned recumbency, particularly in patients with documented supine hypertension 1.
Key points to consider when prescribing midodrine include:
- Monitoring patients regularly for signs of excessive vasoconstriction
- Adjusting the dosage or changing the medication if necessary
- Avoiding the use of midodrine in patients with certain medical conditions, such as supine hypertension or peripheral vascular disease
- Educating patients on the potential risks and benefits of midodrine, including the risk of peripheral cyanosis and paresthesia 1.
It is essential to note that midodrine is the only medication approved by the Food and Drug Administration for the treatment of symptomatic orthostatic hypotension, and its use should be carefully considered in the context of each patient's individual needs and medical history 1.
From the FDA Drug Label
The most frequent adverse reactions seen in controlled trials were supine and sitting hypertension; paresthesia and pruritus, mainly of the scalp; goosebumps; chills; urinary urge; urinary retention and urinary frequency Paresthesia Other adverse reactions that occurred rarely were ... skin hyperesthesia; ... leg cramps.
The FDA drug label mentions paresthesia as a frequent adverse reaction, but it does not specify the location of paresthesia as the upper limbs. It also mentions skin hyperesthesia and leg cramps as rare adverse reactions, but does not provide information on peripheral cyanosis. Therefore, based on the available information, it can be said that long-term use of midodrine may cause paresthesia, but the location is not specified, and there is no direct information on peripheral cyanosis or paresthesia in the upper limbs 2.
From the Research
Adverse Effects of Midodrine
- The most commonly reported adverse events associated with midodrine therapy include piloerection, pruritus, paresthesias, urinary retention, and chills 3.
- Piloerector reactions, gastrointestinal disorders, and cardiovascular complaints are also common adverse effects, but are generally mild and can be controlled by reducing the dosage of midodrine 4.
- Scalp paresthesia has been reported in one patient as an adverse effect of midodrine therapy 5.
Specific Adverse Effects: Peripheral Cyanosis and Paresthesia
- There is no direct evidence in the provided studies that long-term use of midodrine causes peripheral cyanosis.
- Paresthesias are a known adverse effect of midodrine, but the studies do not specify whether this includes the upper limbs 3, 4, 5.
- One study reported scalp paresthesia in one patient, but it is unclear if this is related to upper limb paresthesia 5.
Long-term Use of Midodrine
- One study evaluated the long-term efficacy and safety of midodrine for up to 3 months in patients with neurogenic orthostatic hypotension, and found that single or combination treatment with midodrine and pyridostigmine was effective and safe 6.
- The study reported mild to moderate adverse events in 11.5% of patients, but did not specify whether these included peripheral cyanosis or upper limb paresthesia 6.