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  • CLASSES

    Alopecia Agents
    Arteriolar Smooth Muscle Drugs

    BOXED WARNING

    Acute myocardial infarction, angina, cardiac disease, cardiac tamponade, cerebrovascular disease, coronary artery disease, hypotension, orthostatic hypotension, pericardial effusion, peripheral edema, requires a specialized care setting

    Systemic minoxidil is a potent vasodilator with potential to produce hypotension and reflex tachycardia; serious complications may occur. Minoxidil is relatively contraindicated in patients with cardiac disease (including angina, coronary artery disease, recent or acute myocardial infarction), or cerebrovascular disease because a reflex increase in heart rate and decrease in blood pressure can exacerbate these conditions. Minoxidil is relatively contraindicated in patients with coronary insufficiency, including angina, to avoid the risk of reflex tachycardia and angina exacerbation. Minoxidil may cause pericardial effusion which occasionally may progress to cardiac tamponade. Reserve oral minoxidil for hypertension in patients who do not respond adequately to maximum therapeutic doses of a diuretic (loop diuretic suggested) concurrently with 2 other antihypertensive agents. In experimental animals, minoxidil has been shown to induce several types of myocardial lesions as well as other adverse cardiac effects. Minoxidil must be administered under close supervision, usually in combination with therapeutic doses of a beta-blocker to prevent reflex tachycardia and increased myocardial workload. Minoxidil is often given with a diuretic (preferably a diuretic which acts within the ascending limb of the loop of Henle) to prevent fluid accumulation and peripheral edema. When first administering minoxidil to patients with malignant hypertension and those already receiving guanethidine to avoid rapid or large orthostatic reductions in blood pressure, minoxidil use requires a specialized care setting, specifically hospitalization. Although minoxidil does not directly cause orthostatic hypotension, administration to patients receiving guanethidine can result in profound orthostatic effects. When possible, guanethidine should be discontinued well before minoxidil is initiated. Otherwise, minoxidil therapy should be started in the hospital; the patient should remain hospitalized until the risk of excessive orthostatic effects is minimized and the patient is able to avoid activities that induce orthostatic hypotension.

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Oral antihypertensive agent; topical agent used for alopecia; oral therapy mainly used for patients with severe, drug-resistant HTN due to high potency and significant adverse reactions.

    COMMON BRAND NAMES

    Loniten, Rogaine

    HOW SUPPLIED

    Loniten/Minoxidil Oral Tab: 2.5mg, 10mg
    Minoxidil/Rogaine Topical Sol: 2%, 5%
    Rogaine Topical Foam: 5%

    DOSAGE & INDICATIONS

    For the treatment of alopecia.
    for alopecia androgenetica.
    Topical dosage (2% minoxidil topical solution)
    Adult men and women

    Apply 1 ml twice daily topically, to area where hair growth is desired. Maximum dosage is 2 ml/day applied topically.

    Topical dosage (5% minoxidil topical solution)
    Adult men

    Apply 1 ml twice daily topically, to area where hair growth is desired. Maximum dosage is 2 ml/day applied topically.

    Topical dosage (5% minoxidil aerosol foam)
    Adult men

    Apply one-half capful twice daily topically, to area where hair growth is desired. Maximum dosage is 1 capful/day applied topically.

    for alopecia areata†.
    Topical dosage (5% minoxidil topical solution)
    Adult men and women

    1 ml twice daily topically led to terminal hair regrowth in 29 of 36 patients (81%) with extensive scalp hair loss.

    for chemotherapy-induced alopecia†.
    Topical dosage (2% minoxidil topical solution)
    Adult women

    1 ml twice daily applied topically throughout chemotherapy and up to 4 months post-chemotherapy decreased the duration of alopecia caused by treatment with fluorouracil, doxorubicin, cyclophosphamide. The period of baldness was shortened by a mean of 50.2 days.

    for traction alopecia†.
    Topical dosage (2% minoxidil topical solution)
    Adult women

    1 ml twice daily applied topically was found to be effective in two case reports. New hair growth was visible after 3 months of treatment, and convincing growth was evident at 6—9 months of continuous treatment.

    for prevention of hair shedding following hair transplantation.
    Topical dosage (2% minoxidil topical solution)
    Adult men

    1 ml twice daily applied topically reduced postoperative shedding and improved regrowth of hair in a study of 16 patients with androgenetic alopecia undergoing hair transplantation. Minoxidil was used for 4 weeks prior to surgery, stopped for 3 weeks, and then resumed again for 3 months.

    For the treatment of hypertension that is symptomatic or associated with target organ damage and is not manageable with other maximum therapeutic doses of diuretic plus two other antihypertensive agents.
    NOTE: Minoxidil is not indicated for initial therapy of mild forms of hypertension.
    NOTE: Minoxidil should be administered under close medical supervision, usually concomitantly with therapeutic doses of a beta-adrenergic blocking agent to prevent tachycardia and increased myocardial workload. Minoxidil should also be given concomitantly with a diuretic and salt restriction to prevent serious fluid accumulation.
    NOTE: In general, >= 3 days should elapse between dosage adjustments. However, when rapid management of hypertension is indicated, doses may be adjusted every 6 hours with careful monitoring.
    Oral dosage
    Adults and Adolescents

    Initially, 5 mg PO, given as a single daily dose. The dosage may be increased in intervals of at least 3 days to 10, 20, and then to 40 mg in single or divided doses for optimum blood pressure control. The usual effective dose range is 10—40 mg/day, given in 1—2 divided doses. If supine diastolic pressure has decreased < 30 mm Hg, administer total daily dose once per day; if supine diastolic pressure has decreased >= 30 mm Hg, the daily dosage should be divided into 2 equal doses.

    Geriatric

    See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.

    Children < 12 years

    Initially, 0.2 mg/kg (up to 5 mg) PO, given as a single daily dose. Titrate by 0.1— 0.2 mg/kg/day at intervals >= 3 days if needed to attain clinical goals. The usual effective dose range is 0.25—1 mg/kg/day, given as 1 dose or 2 divided doses.

    For the treatment of anal fissures†.
    Topical dosage (0.5% minoxidil in white paraffin base)
    Adults and Adolescents

    0.5 grams of 0.5% minoxidil and 5% lignocaine ointment applied every 8 hours circumferentially inside the anus for 6 weeks. Mean time to complete healing was significantly shorter with combination treatment than with either drug alone.

    For the treatment of hypertension and the subsequent decline in renal function associated with scleroderma renal crisis (SRC)†.
    Oral dosage
    Adults

    Initially, 5 mg/day PO, given as 1 dose or 2 divided doses. Increase after 3 days by 10—20 mg/day to reach desired blood pressure. Maximum dosage is 100 mg/day.

    Geriatric

    See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    100 mg/day PO, 2 ml/day of topical solution to scalp, or 1 capful/day of topical foam to scalp.

    Elderly

    100 mg/day PO, 2 ml/day of topical solution to scalp, or 1 capful/day of topical foam to scalp.

    Adolescents

    100 mg/day PO.

    Children

    50 mg/day PO.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage should be modified depending on clinical response and degree of hepatic impairment, but no quantitative recommendations are available.

    Renal Impairment

    CrCl > 50 ml/min: No dosage adjustment needed.
    CrCl 10—50 ml/min: Extend the dosage interval to once every 24 hours.
    CrCl < 10 ml/min: Not recommended.

    ADMINISTRATION

    NOTE: Oral minoxidil must be administered under close supervision due to the risk of excessive hypotension, reflex tachycardia, and angina.
     

    Oral Administration

    Minoxidil may be administered without regard to meals.

    Topical Administration

    Minoxidil topical solution or foam should only be applied to the scalp. Instruct patient on the proper application technique and give written instructions supplied by the manufacturer.
    Prior to administration, the hair and scalp should be dry. If applied with fingertips, wash hands thoroughly after applying. If the metered-spray applicator is used, avoid inhalation of the mist.

    STORAGE

    Loniten:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Rogaine:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Minoxidil is contraindicated in patients with a history of minoxidil hypersensitivity.
     
    Minoxidil has been reported to produce cardiac lesions in animals. Some lesions are characteristic of other drugs that can cause tachycardia and/or hypotension (e.g., isoproterenol, hydralazine). These effects are more likely to occur in patients with compromised renal function and in patients with connective tissue disease, uremic syndrome, CHF, or minoxidil-induced fluid retention.

    Acute myocardial infarction, angina, cardiac disease, cardiac tamponade, cerebrovascular disease, coronary artery disease, hypotension, orthostatic hypotension, pericardial effusion, peripheral edema, requires a specialized care setting

    Systemic minoxidil is a potent vasodilator with potential to produce hypotension and reflex tachycardia; serious complications may occur. Minoxidil is relatively contraindicated in patients with cardiac disease (including angina, coronary artery disease, recent or acute myocardial infarction), or cerebrovascular disease because a reflex increase in heart rate and decrease in blood pressure can exacerbate these conditions. Minoxidil is relatively contraindicated in patients with coronary insufficiency, including angina, to avoid the risk of reflex tachycardia and angina exacerbation. Minoxidil may cause pericardial effusion which occasionally may progress to cardiac tamponade. Reserve oral minoxidil for hypertension in patients who do not respond adequately to maximum therapeutic doses of a diuretic (loop diuretic suggested) concurrently with 2 other antihypertensive agents. In experimental animals, minoxidil has been shown to induce several types of myocardial lesions as well as other adverse cardiac effects. Minoxidil must be administered under close supervision, usually in combination with therapeutic doses of a beta-blocker to prevent reflex tachycardia and increased myocardial workload. Minoxidil is often given with a diuretic (preferably a diuretic which acts within the ascending limb of the loop of Henle) to prevent fluid accumulation and peripheral edema. When first administering minoxidil to patients with malignant hypertension and those already receiving guanethidine to avoid rapid or large orthostatic reductions in blood pressure, minoxidil use requires a specialized care setting, specifically hospitalization. Although minoxidil does not directly cause orthostatic hypotension, administration to patients receiving guanethidine can result in profound orthostatic effects. When possible, guanethidine should be discontinued well before minoxidil is initiated. Otherwise, minoxidil therapy should be started in the hospital; the patient should remain hospitalized until the risk of excessive orthostatic effects is minimized and the patient is able to avoid activities that induce orthostatic hypotension.

    Heart failure, pulmonary hypertension, renal disease, renal failure, renal impairment

    Minoxidil is relatively contraindicated in patients with renal disease, preexisting pulmonary hypertension, or chronic congestive heart failure not secondary to hypertension because the drug can cause an increase in pulmonary artery pressure, which could be detrimental to these patients. Use of minoxidil has been associated with the development of pericardial effusion and tamponade in some patients, and it may be more likely to occur in patients with renal disease. Since approximately only 10% of active drug is eliminated unchanged via the kidneys, minoxidil can be used safely in patients with renal impairment. Renal elimination, however, may be reduced and dosage adjustment may be necessary. Avoid use of minoxidil in patients with severe renal failure (CrCl < 10 ml/min).

    Pregnancy

    Minoxidil is classified as pregnancy risk category C. Although no adequate human studies have examined the effects of this drug on the fetus, animal reproduction studies have shown adverse effects, including reduced ability to conceive and a reduced survival of offspring. Dysmorphic facial features and hypertrichosis were observed in an infant whose mother received a daily minoxidil dosage of 10 mg during pregnancy. Therefore, in making the decision to administer this drug during pregnancy, the potential risks to the fetus and possible difficulty in conceiving must be weighed against the potential benefits to the mother.

    Breast-feeding

    According to the manufacturer, minoxidil should not be administered to a nursing mother. The American Academy of Pediatrics (AAP) considers minoxidil to be generally compatible with breast-feeding ; however, other experts are less comfortable with the use of this potent antihypertensive agent in nursing mothers. In one case report of a woman taking minoxidil 5 mg PO twice daily, minoxidil was rapidly excreted into the breast milk. After two months, no adverse events were reported in the nursing infant. The effect of prolonged exposure during breast-feeding is unknown. Examples of other antihypertensives with more data in this population that have been classified as usually compatible with breast-feeding by the AAP and may be possible alternatives for some patients include enalapril, hydrochlorothiazide, methyldopa, and propranolol. It is not known whether topical minoxidil is distributed into breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children

    The safety and efficacy of topical minoxidil products have not been established in children and adolescents.

    Pheochromocytoma

    Minoxidil is contraindicated in patients with pheochromocytoma because the hypotensive effects of the drug can stimulate catecholamine secretion.

    Skin abrasion

    Systemic effects resulting from topically administered minoxidil are unlikely but theoretically could occur if the drug is overused. Skin abrasion or irritations, such as excoriations, psoriasis, or sunburn, can increase the systemic absorption of topically administered minoxidil.

    Geriatric

    Reported clinical experience has not identified differences in responses in geriatric adults vs. younger adult patients. In general, systemic dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Topical minoxidil use carries no special precaution in the elderly, but any patient experiencing dizziness or faintness should discontinue topical use. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. There are many drug interactions that can potentiate the effects of antihypertensives. Some agents require a gradual taper to avoid adverse consequences caused by abrupt discontinuation.

    ADVERSE REACTIONS

    Severe

    pericardial effusion / Delayed / 3.0-3.0
    heart failure / Delayed / Incidence not known
    cardiac tamponade / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known

    Moderate

    edema / Delayed / 7.0-7.0
    peripheral edema / Delayed / Incidence not known
    sodium retention / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    angina / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    erythema / Early / Incidence not known

    Mild

    mastalgia / Delayed / 0-1.0
    headache / Early / Incidence not known
    hypertrichosis / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    xerosis / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acrivastine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Aldesleukin, IL-2: (Moderate) Vasodilators may potentiate the hypotension seen with aldesleukin, IL 2.
    Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
    Aliskiren: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Amlodipine: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Valsartan: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as the vasodilators, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents. Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure.
    Amifostine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
    Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
    Amphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Amphetamine; Dextroamphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Amyl Nitrite: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Apomorphine: (Moderate) Concurrent use of apomorphine and vasodilators can cause greater decreases in blood pressure than use of apomorphine alone. Patients receiving a combination of apomorphine and vasodilators should be closely monitored for hypotension and orthostasis.
    Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
    Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Articaine; Epinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) Use of vasodilators and ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside for supportive care of ergot alkaloid toxicity. Care must be taken to avoid aggravating an already existent hypotension occurring with ergot overdose.
    Benzphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Brompheniramine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Caffeine; Ergotamine: (Minor) Use of vasodilators and ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside for supportive care of ergot alkaloid toxicity. Care must be taken to avoid aggravating an already existent hypotension occurring with ergot overdose.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
    Cetirizine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
    Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
    Codeine; Phenylephrine; Promethazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
    Conjugated Estrogens: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Desloratadine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dexmedetomidine: (Moderate) Concomitant administration of dexmedetomidine and vasodilators could lead to additive hypotension and bradycardia; use together with caution. In clinical trials where vasodilators were co-administered with dexmedetomidine an additive pharmacodynamic effect was not observed. However, both vasodilators and dexmeditomidine may cause symptomatic hypotension. If hypotension occurs, dose reduction of one or both drugs may be needed and supportive measures instituted.
    Dexmethylphenidate: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextroamphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Dienogest; Estradiol valerate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Diethylpropion: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Diethylstilbestrol, DES: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dihydroergotamine: (Minor) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dobutamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dopamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Drospirenone; Estradiol: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Drospirenone; Ethinyl Estradiol: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
    Enflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Ephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Epinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Epoprostenol: (Major) Further reductions in blood pressure may occur when vasodilators are combined with epoprostenol.
    Ergonovine: (Minor) Use of vasodilators and ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside used for supportive care of ergot alkaloid toxicity.
    Ergotamine: (Minor) Use of vasodilators and ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside for supportive care of ergot alkaloid toxicity. Care must be taken to avoid aggravating an already existent hypotension occurring with ergot overdose.
    Esterified Estrogens: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Esterified Estrogens; Methyltestosterone: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estradiol: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estradiol; Levonorgestrel: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estradiol; Norethindrone: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estradiol; Norgestimate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estradiol; Progesterone: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estrogens: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Estropipate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Desogestrel: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Etonogestrel: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Levonorgestrel: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Norethindrone: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Norgestimate: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Ethinyl Estradiol; Norgestrel: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Fexofenadine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Fluoxetine; Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Fospropofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Haloperidol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
    Halothane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Hawthorn, Crataegus laevigata: (Moderate) Hawthorn, Crataegus laevigata may lower peripheral vascular resistance. Hawthorn use in combination with vasodilators may lead to additional reductions in blood pressure in some individuals. Patients receiving hawthorn concurrently with antihypertensive medications should receive periodic blood pressure monitoring.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Ibuprofen; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Iloprost: (Moderate) Vasodilators may have additive hypotensive effects when given with other antihypertensive agents.
    Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Isoproterenol: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Levomilnacipran: (Moderate) Levomilnacipran has been associated with an increase in blood pressure. The effectiveness of minoxidil may be diminished during concurrent use of levomilnacipran. It is advisable to monitor blood pressure if the combination is necessary.
    Lisdexamfetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Lofexidine: (Major) Because the central alpha-2 agonist effects of lofexidine can cause hypotension and orthostasis, the drug should be avoided, if possible, in combination with other medications that can decrease blood pressure such as systemic vasodilators. If coadministration is required, blood pressure should be monitored, particularly after dose changes of either agent. Adjustments should be made as clinically indicated.
    Loratadine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Mepivacaine; Levonordefrin: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Mestranol; Norethindrone: (Minor) Estrogens can cause fluid retention, increasing blood pressure and thereby antagonizing the antihypertensive effects of minoxidil.
    Methamphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
    Methylphenidate: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Midodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Milnacipran: (Moderate) Milnacipran has been associated with an increase in blood pressure. The effectiveness of antihypertensive agents may be diminished during concurrent use of milnacipran. It is advisable to monitor blood pressure if the combination is necessary.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    Naproxen; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Nesiritide, BNP: (Moderate) The potential for hypotension may be increased when coadministering nesiritide with vasodilators. Reduce the dose of or discontinue nesiritide in patients who develop hypotension. In clinical trials, no drug interactions were detected except for an increase in symptomatic hypotension in patients receiving afterload reducers, such as vasodilators.
    Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Norepinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by vasodilators. Also vasodilators can antagonize the effectiveness of oxymetazoline. If these drugs are used together, closely monitor for changes in blood pressure.
    Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and minoxidil who are susceptible to hypotension.
    Pemoline: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
    Phendimetrazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phenelzine: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Phentermine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phentermine; Topiramate: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phenylephrine; Promethazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
    Prilocaine; Epinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Procaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Racepinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Ritodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Selegiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Sympathomimetics: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
    Thiopental: (Moderate) Additive hypotensive effects may occur when vasodilators are used concomitantly with thiopental. Dosages should be adjusted carefully, according to blood pressure.
    Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
    Tranylcypromine: (Severe) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
    Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
    Yohimbine: (Moderate) Yohimbine can increase blood pressure and therefore can antagonize the therapeutic action of antihypertensive agents. Use with particular caution in hypertensive patients with high or uncontrolled BP.
    Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

    PREGNANCY AND LACTATION

    Pregnancy

    Minoxidil is classified as pregnancy risk category C. Although no adequate human studies have examined the effects of this drug on the fetus, animal reproduction studies have shown adverse effects, including reduced ability to conceive and a reduced survival of offspring. Dysmorphic facial features and hypertrichosis were observed in an infant whose mother received a daily minoxidil dosage of 10 mg during pregnancy. Therefore, in making the decision to administer this drug during pregnancy, the potential risks to the fetus and possible difficulty in conceiving must be weighed against the potential benefits to the mother.

    According to the manufacturer, minoxidil should not be administered to a nursing mother. The American Academy of Pediatrics (AAP) considers minoxidil to be generally compatible with breast-feeding ; however, other experts are less comfortable with the use of this potent antihypertensive agent in nursing mothers. In one case report of a woman taking minoxidil 5 mg PO twice daily, minoxidil was rapidly excreted into the breast milk. After two months, no adverse events were reported in the nursing infant. The effect of prolonged exposure during breast-feeding is unknown. Examples of other antihypertensives with more data in this population that have been classified as usually compatible with breast-feeding by the AAP and may be possible alternatives for some patients include enalapril, hydrochlorothiazide, methyldopa, and propranolol. It is not known whether topical minoxidil is distributed into breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Minoxidil has a direct vasodilatory effect on arterial smooth muscle, causing a reduction in peripheral resistance and blood pressure. Minoxidil does not exhibit CNS or adrenergic neuronal blocking effects; minoxidil retains its activity despite adrenergic denervation. Cyclic adenosine monophosphate (cAMP) may contribute to relaxation of vascular smooth muscle. Minoxidil-induced delay in the hydrolysis of cAMP via inhibition of phosphodiesterase may contribute to the drug's vasodilatory action.All direct vasodilators produce a sympathetic response including an increase in heart rate, stroke volume, and cardiac output, and a marked increase in plasma renin activity, which, in turn, leads to increased sodium and water retention. This increased renin release is believed to be partially mediated by the beta-adrenergic system. These compensatory responses tend to diminish the hypotensive effects of minoxidil. Additional therapeutic effects can be achieved by using a beta-blocker to offset the predictable sympathetic stimulation caused by minoxidil. Methyldopa may be used if beta-blocker therapy is contraindicated; however, because of its delay in onset, methyldopa must be initiated 24 hours prior to initiating minoxidil. Vasodilator-induced fluid retention is somewhat related to the potency of the vasodilator. Due to its potency, fluid retention occurs routinely with minoxidil. Often, this fluid retention requires concomitant use of loop diuretics (see Adverse Reactions). Triple-drug therapy consisting of a loop diuretic, beta-blocker, and minoxidil produces prompt, sustained reduction in blood pressure in patients with severe hypertension. Minoxidil preferentially dilates arterioles; therefore, postural hypotension may occur during therapy. As an antihypertensive, minoxidil does not lead to improvements in LVH. Minoxidil may actually worsen LVH, potentially due to reflex tachycardia and sympathetic stimulation, which may counteract the benefits of afterload reduction. Minoxidil does not affect glucose tolerance or serum lipids.The exact mechanism responsible for minoxidil-induced hair growth is not known, but appears to be independent of vasodilation. While systemic therapy will stimulate hair growth, topical therapy usually does not cause hypotension. Current evidence suggests the primary action of topical minoxidil is to decrease the latent period of the hair cycle. The latent period (the time between shedding of telogen hair and the onset of the next anagen) is typically prolonged in male pattern balding; however, this effect has not been demonstrated in balding females. Calcium may also be involved in the process of hair regrowth. In the presence of calcium, epidermal growth factor (EGF) inhibits hair growth. The entry of calcium into a hair cell is opposed by potassium channel openers, such as minoxidil; therefore, EGF-induced inhibition of hair will be opposed by the action of minoxidil, and hair will grow more proficiently. Biopsy specimens have not demonstrated evidence of new follicle formation with the use of minoxidil. Furthermore, minoxidil appears to affect only suboptimal follicles with no further stimulation of normal hair follicles. Minoxidil also may alter the metabolism of androgens in the scalp. Minoxidil increases 17 beta-hydroxylated dehydrogenase activity by almost 40% in dermal papilla cells of a balding scalp, whereas the effect is much less in a nonbalding scalp. Whether this modification in testosterone metabolism of cells of a balding scalp is related to the therapeutic effect of minoxidil is unknown.

    PHARMACOKINETICS

    Minoxidil is administered orally and topically. Minoxidil distributes widely throughout the body tissues and is extensively metabolized in the liver. Both the unchanged drug and its metabolites (primarily the glucuronide conjugate) are excreted in the urine.
     
    Minoxidil is not significantly bound to plasma proteins; it is freely filtered and undergoes no tubular secretion. Thus, renal clearance corresponds to glomerular filtration and accounts for approximately 10% of total clearance. In addition, little drug accumulation occurs in patients with renal insufficiency, perhaps due to a combination of minimal renal clearance and rapid hepatic metabolism.

    Oral Route

    Approximately 90% of an oral dose of minoxidil is absorbed from the GI tract. Antihypertensive effects begin within 30 minutes of oral administration, and, although the plasma half-life is approximately 4 hours, antihypertensive effects can last 75 hours. Despite the prolonged duration of action, no drug is detected in the plasma after 24 hours. This prolonged duration of effect may be explained by drug retention in vascular smooth muscle tissues.

    Topical Route

    Topical minoxidil is poorly absorbed through the skin; the systemic absorption averages 2% (range 0.3—4.5%). Roughly 95% of a topical dose will be eliminated after 4 days.