What is the maximum dose for hydralazine?

From the Guidelines

The maximum dose for hydralazine is 300 mg daily in divided doses.

Key Points

• The maximum dose of hydralazine can be found in several studies, including 1 and 1, which both report a maximum dose of 300 mg daily in divided doses.
• Another study, 1, reports a maximum dose of 75 mg 3 daily, but this appears to be a lower dose than the maximum dose reported in the other studies.
• The study 1 also reports a maximum dose of 75 mg hydralazine TID, which is equivalent to 225 mg daily.
• However, based on the highest quality study, 1 is a more recent study, but it seems to have a lower maximum dose, whereas 1 and 1 are older studies but have a higher maximum dose, and considering the context of real-life clinical medicine, the higher dose is chosen for the maximum dose.
• It's worth noting that the dosing of hydralazine can vary depending on the specific clinical context and the patient's response to treatment, and the dose should be titrated to achieve the desired therapeutic effect while minimizing adverse effects.
• The fixed-dose combination of isosorbide dinitrate and hydralazine has a maximum dose of 40 mg isosorbide dinitrate/75 mg hydralazine TID, which is equivalent to 120 mg isosorbide dinitrate/225 mg hydralazine daily 1.

From the FDA Drug Label

The usual recommended oral starting dosage is 0.75 mg/kg of body weight daily in four divided doses. Dosage may be increased gradually over the next 3 to 4 weeks to a maximum of 7. 5 mg/kg or 200 mg daily. The maximum dose for hydralazine is 200 mg daily or 7.5 mg/kg of body weight daily 2.

• The maximum dose is based on the patient's body weight, with a maximum of 7.5 mg/kg or a fixed dose of 200 mg daily.

From the Research

Maximum Dose for Hydralazine

• The maximum dose for hydralazine is not more than 200 mg daily, as stated in the study published in the British medical journal (Clinical research ed.) 3.
• This dose restriction is due to the risk of inducing the lupus syndrome, which has been shown to be dose-dependent.
• Another study published in the Journal of pharmacokinetics and biopharmaceutics 4 analyzed the dose-response curve of hydralazine and found that daily doses of 75,150, or 300 mg were used in the study, but the maximum recommended dose is still 200 mg daily.

Dose-Response Relationship

• The study published in the British medical journal (Clinical research ed.) 3 found that the incidence of the lupus syndrome was 5.4% with 100 mg daily and 10.4% with 200 mg daily.
• The study published in the Journal of pharmacokinetics and biopharmaceutics 4 found that the maximum antihypertensive response (Emax) to hydralazine was 9.4 mm Hg, and the daily dose that elicited 50% of the maximum response (D50) was 0.87 mg/kg for slow acetylators and 1.68 mg/kg for fast acetylators.

Acetylator Status

• The study published in the International journal of clinical pharmacology and therapeutics 5 found that the dose of hydralazine needs to be adjusted for the acetylation status of patients, with slow acetylators requiring a lower dose than fast acetylators.
• The study published in the Journal of pharmacokinetics and biopharmaceutics 4 also found that acetylator class was an important factor in the dose-response relationship of hydralazine.