Anti-hypertensive (Other Agents)

Aliskiren (Tekturna®)

Drug Category: Renin Inhibitor. Indication: Treatment of hypertension, alone or in combination with other antihypertensive agents.

Dosing (Adults):
Hypertension: Initial: 150 mg once daily; may increase to 300 mg once daily (maximum: 300 mg/day). Note: Prior to initiation, correct hypovolemia and/or closely monitor volume status in patients on concurrent diuretics during treatment
initiation.

Renal dosing:
Mild-to-moderate impairment [GFR >30 mL/minute and/or Scr <1.7 mg/dL (women); Scr <2 mg/dL (men)]: No dose adjustment required. Severe impairment [GFR<30 mL/minute and/or Scr >1.7 mg/dL (women); Scr >2 mg/dL (men)]: Use caution; not studied in severe renal impairment.

Administration: Administer at the same time daily; may take with or without a meal, but consistent administration with regards to meals is recommended. Avoid taking with high-fat meals.

Supplied: Tablet: 150 mg, 300 mg

bosentan (tracleer ®)

Endothelin receptor antagonist.
Adult (usual) Pulmonary arterial hypertension (PAH): initial, 62.5 mg po bid x 4 weeks. Maintenance (PAH): up to 125 mg po bid. Doses above 125 mg b.i.d. did not appear to confer additional benefit sufficient to offset the increased risk of liver injury.

Monitoring: monitor liver function before and during therapy. Monitor hemoglobin levels after 1 and 3 months, then every 3 months monthly.
[Supplied: 62.5, 125 mg tablets]

epoprostenol (Flolan ®)

Epoprostenol (PGI2, prostacyclin): a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation. Indication: long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.
Dosage - Adult (usual) Pulmonary hypertension: initial, 2 ng/kg/min IV, titrate upward in increments of 2 ng/kg/min every 15 min or longer until dose-limiting pharmacological effects are elicited or until tolerance develops.
Administration: reconstitute only with supplied diluent; do not give with other parenteral medications. Infuse continuous chronic infusion via a central venous catheter with an ambulatory infusion pump - may be administered peripherally until central catheter established. Avoid abrupt withdrawal. Anticipate need for periodic dose adjustments.

fenoldopam (Corlopam ®)

Indications: short-term (up to 48 hours) management of severe hypertension when rapid, but quickly reversible, emergency reduction of blood pressure is clinically indicated, including malignant hypertension with deteriorating end-organ function.

Dosage (adult): Hypertension: initial 0.03-0.1 mcg/kg/min IV; increase every 15 min by 0.05-0.1 mcg/kg/min based on response. Maximum: 1.6 mcg/kg/min. In clinical trials, doses from 0.01-1.6 µg/kg/min have been studied. Most of the effect of a given infusion rate is attained in 15 minutes. A bolus dose should not be used. Hypotension and rapid decreases of blood pressure should be avoided. The initial dose should be titrated upward or downward, no more frequently than every 15 minutes (and less frequently as goal pressure is approached) to achieve the desired therapeutic effect. The recommended increments for titration are 0.05-0.1 µg/kg/min.

[Supplied: 10 mg/ml solution]

hydralazine (Apresoline ®)

Direct arteriolar vasodilator with little or no effect on the venous circulation. Precautions are needed in patients with underlying coronary disease or an aortic dissection. Beta-blocker should be given concurrently to minimize reflex sympathetic stimulation. The hypotensive response to hydralazine is less predictable than that seen with other parenteral agents.

Dosing (Adult): Initial (Acute hypertension): 10 mg slow IV bolus ( maximum dose being 20 mg) every 4 to 6 hours as needed. May increase to 40 mg/dose. Change to oral therapy as soon as possible. The fall in blood pressure begins within 10 to 30 minutes and lasts 2 to 4 hours. May also be given IM.

Hypertension (Oral): Initial: 10 mg 4 times/day. Increase by 10-25 mg/dose every 2-5 days (maximum: 300 mg/day). Usual dose range (JNC 7): 25-100 mg/day in 2 divided doses.

Pre-eclampsia/eclampsia: 5 mg/dose (IM, IV) then 5-10 mg every 20-30 minutes as needed.

CHF: Initial dose: 10-25 mg orally 3-4 times/day. Dosage must be adjusted based on individual response. Target dose: 75 mg 4 times daily in combination with isosorbide dinitrate (40 mg 4 times daily). Range: Typically 200-600 mg daily in 2-4 divided doses. Dosages as high as 3 grams per day have been used in some patients for symptomatic and hemodynamic improvement.

Renal dosing: crcl 10-50 ml/min: Administer every 8 hours. crcl <10 ml/min: Administer every 8 to 16 hours in fast acetylators and every 12-24 hours in slow acetylators.

Supplied: Injection (soln): 20 mg/ml (1 ml vial). Tablet: 10 mg, 25 mg, 50 mg, 100 mg.

minoxidil (Loniten ®)

Severe Hypertension: initial, 5 mg/day orally as single dose or 2 divided doses. Maintenance (HTN): 10-40 mg/day orally daily in 1-2 divided doses (Maximum: 100 mg/day) . Acts directly on vascular smooth muscle with selective vasodilatation of the arteriolar resistance vessels and little or no effects on venous capacitance vessels and does not effect the functioning of the carotid or aortic baroreceptors.

[Supplied: 2.5, 5, 10mg tablet]

nitroprusside (Nipride ®)

Dosing (Adult): Initial: 0.3 to 0.5 mcg/kg/min. Increase in increments of 0.5 mcg/kg/min while titrating to desired hemodynamic effect. Dosage rates well within the product labeling have resulted in toxicity.

Additionally, dosage rates that are well tolerated over a short course of therapy may be toxic over prolonged therapy. Infusion rates of 2 mcg/kilogram/minute are suggested as safe, while rates greater than 4 micrograms/kilogram/minute may lead to cyanide toxicity within 3 hours. The range is 0.3 to 10 mcg/kilogram/minute. Doses exceeding 10 mcg/kg/min are rarely required.

phentolamine (regitine ®)

Extravasation - norepinephrine: 5-10 mg in 10 mL saline SC infiltrated within 12 hours into area of extravasation.
Hypertensive crisis: 5-20 mg IV.
Pheochromocytoma (diagnosis): 5 mg IV or IM.
Tissue necrosis prevention: 10 milligrams may be added to each liter of solution containing norepinephrine to prevent dermal necrosis and sloughing associated with intravenous administration of norepinephrine.

treprostinil (Remodulin ®)

Indications: Pulmonary arterial hypertension (PAH) in patients with NYHA Class II-IV symptoms.
Dosage: Pulmonary arterial hypertension: initial, 1.25 ng/kg/min continuous SC infusion; decrease to 0.625 ng/kg/min if initial dose cannot be tolerated. Pulmonary arterial hypertension: adjustments, increase dose in increments of no more than 1.25 ng/kg/min per week for the first 4 weeks and then no more than 2.5 ng/kg/min per week for remaining duration.
Administration: administer by continuous subcutaneous infusion to diminish symptoms associated with exercise. avoid abrupt cessation of infusion. Chronic dosage adjustments should establish a dose at which PAH symptoms are improved, while minimizing side effects. Minimal experience with doses greater than 40 ng/kg/min.

[Supplied (20 ml vials) 1, 2.5 , 5, and 10 mg/ml solution]

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David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.

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