Nifedipine (nifedipine 60 mg) Dailymed

Rx only For Oral Use

Description

Nifedipine extended-release tablets are an extended-release tablet dosage form of the calcium channel blocker nifedipine. Nifedipine is 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester. The molecular formula is C₁₇H₁₈N₂O₆ and has the structural formula:

Nifedipine is a yellow crystalline substance, practically insoluble in water but soluble in ethanol. It has a molecular weight of 346.3. Nifedipine extended-release tablets contain 60 mg of nifedipine for once-a-day oral administration.

In addition, each tablet contains the following inactive ingredients: ethylcellulose, ferric oxide yellow, hydroxyethyl cellulose, hypromellose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, polyacrylic dispersion (copolymer of ethyl acrylate and methyl methacrylate), polyethylene glycol, silicon dioxide, sodium lauryl sulfate, talc, and titanium dioxide.

Nifedipine extended-release tablets meet USP Dissolution Test 4.

Clinical Pharmacology

Nifedipine is a calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist) which inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile processes of vascular smooth muscle and cardiac muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Nifedipine selectively inhibits calcium ion influx across the cell membrane of vascular smooth muscle and cardiac muscle without altering serum calcium concentrations.

Mechanism of Action

The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. The increased peripheral vascular resistance, an underlying cause of hypertension, results from an increase in active tension in the vascular smooth muscle. Studies have demonstrated that the increase in active tension reflects an increase in cytosolic free calcium.

Nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. The binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. Stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. The reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure.

Pharmacokinetics and Metabolism

Nifedipine is completely absorbed after oral administration. The bioavailability of nifedipine as nifedipine extended-release tablet relative to immediate-release nifedipine is in the range of 84% to 89%. After ingestion of nifedipine extended-release tablets under fasting conditions, plasma concentrations peak at about 2.5 to 5 hours with a second small peak or shoulder evident at approximately 6 to 12 hours post dose. The elimination half-life of nifedipine administered as nifedipine extended-release tablet is approximately 7 hours in contrast to the known 2 hour elimination half-life of nifedipine administered as an immediate-release capsule.

When nifedipine extended-release tablet is administered as multiples of 30 mg tablets over a dose range of 30 mg to 90 mg, the area under the curve (AUC) is dose proportional; however, the peak plasma concentration for the 90 mg dose given as 3 × 30 mg is 29% greater than predicted from the 30 mg and 60 mg doses.

Two 30 mg nifedipine extended-release tablets may be interchanged with a 60 mg nifedipine extended-release tablet. Three 30 mg nifedipine extended-release tablets, however, result in substantially higher C_max values than those after a single 90 mg nifedipine extended-release tablet. Three 30 mg tablets should, therefore, not be considered interchangeable with a 90 mg tablet.

Once daily dosing of nifedipine extended-release tablets under fasting conditions results in decreased fluctuations in the plasma concentration of nifedipine when compared to t.i.d. dosing with immediate-release nifedipine capsules. The mean peak plasma concentration of nifedipine following a 90 mg nifedipine extended-release tablet, administered under fasting conditions, is approximately 115 ng/mL. When nifedipine extended-release tablet is given immediately after a high fat meal in healthy volunteers, there is an average increase of 60% in the peak plasma nifedipine concentration, a prolongation in the time to peak concentration, but no significant change in the AUC. Plasma concentrations of nifedipine when nifedipine extended-release tablet is taken after a fatty meal result in slightly lower peaks compared to the same daily dose of the immediate-release formulation administered in three divided doses. This may be, in part, because nifedipine extended-release tablet is less bioavailable than the immediate-release formulation.

Nifedipine is extensively metabolized to highly water soluble, inactive metabolites accounting for 60% to 80% of the dose excreted in the urine. Only traces (less than 0.1% of the dose) of the unchanged form can be detected in the urine. The remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion.

Nifedipine is metabolized via the cytochrome P450 3A4 system. Drugs that are known to either inhibit or induce this enzyme system may alter the first pass or clearance of nifedipine.

No studies have been performed with nifedipine extended-release tablets in patients with renal failure; however, significant alterations in the pharmacokinetics of nifedipine immediate-release capsules have not been reported in patients undergoing hemodialysis or chronic ambulatory peritoneal dialysis. Since the absorption of nifedipine from nifedipine extended-release tablets could be modified by renal disease, caution should be exercised in treating such patients.

Because nifedipine is metabolized via the cytochrome P450 3A4 system, its pharmacokinetics may be altered in patients with chronic liver disease. Nifedipine extended-release tablets have not been studied in patients with hepatic disease; however, in patients with hepatic impairment (liver cirrhosis), nifedipine has a longer elimination half-life and higher bioavailability than in healthy volunteers.

The degree of protein binding of nifedipine is high (92% to 98%). Protein binding may be greatly reduced in patients with renal or hepatic impairment.

After administration of nifedipine extended-release tablets to healthy elderly men and women (age >60 years), the mean C_max is 36% higher and the average plasma concentration is 70% greater than in younger patients.

In healthy subjects, the elimination half-life of a different sustained-release nifedipine formulation was longer in elderly subjects (6.7 h) compared to young subjects (3.8 h) following oral administration. A decreased clearance was also observed in the elderly (348 mL/min) compared to young subjects (519 mL/min) following intravenous administration.

Coadministration of nifedipine with grapefruit juice results in up to a 2-fold increase in AUC and C_max due to inhibition of CYP3A related first-pass metabolism. Ingestion of grapefruit and grapefruit juice should be avoided while taking nifedipine.

Clinical Studies

Nifedipine extended-release tablets produced dose-related decreases in systolic and diastolic blood pressure as demonstrated in two double-blind, randomized, placebo-controlled trials in which over 350 patients were treated with nifedipine extended-release tablets, 30, 60 or 90 mg once daily for 6 weeks. In the first study, nifedipine extended-release tablet was given as monotherapy and in the second study, nifedipine extended-release tablet was added to a beta-blocker in patients not controlled on a beta-blocker alone. The mean trough (24 hours post-dose) blood pressure results from these studies are shown below:

MEAN REDUCTIONS IN TROUGH SUPINE BLOOD PRESSURE (mmHg)

	SYSTOLIC/DIASTOLIC
NIFEDIPINE EXTENDED-RELEASE DOSE	N	MEAN TROUGH REDUCTION
STUDY 1
30 mg	60	5.3/2.9
60 mg	57	8.0/4.1
90 mg	55	12.5/8.1
STUDY 2
30 mg	58	7.6/3.8
60 mg	63	10.1/5.3
90 mg	62	10.2/5.8

The trough/peak ratios estimated from 24 hour blood pressure monitoring ranged from 41% to 78% for diastolic and 46% to 91% for systolic blood pressure.

Hemodynamics

Like other slow-channel blockers, nifedipine exerts a negative inotropic effect on isolated myocardial tissue. This is rarely, if ever, seen in intact animals or man, probably because of reflex responses to its vasodilating effects. In man, nifedipine decreases peripheral vascular resistance which leads to a fall in systolic and diastolic pressures, usually minimal in normotensive volunteers (less than 5 to 10 mmHg systolic), but sometimes larger. With nifedipine extended-release tablets, these decreases in blood pressure are not accompanied by any significant change in heart rate. Hemodynamic studies of the immediate-release nifedipine formulation in patients with normal ventricular function have generally found a small increase in cardiac index without major effects on ejection fraction, left ventricular end-diastolic pressure (LVEDP), or volume (LVEDV). In patients with impaired ventricular function, most acute studies have shown some increase in ejection fraction and reduction in left ventricular filling pressure.

Electrophysiologic Effects

Although, like other members of its class, nifedipine causes a slight depression of sinoatrial node function and atrioventricular conduction in isolated myocardial preparations, such effects have not been seen in studies in intact animals or in man. In formal electrophysiologic studies, predominantly in patients with normal conduction systems, nifedipine administered as the immediate-release capsule has had no tendency to prolong atrioventricular conduction or sinus node recovery time, or to slow sinus rate.

Indications And Usage

Nifedipine extended-release tablets are indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

Contraindications

Concomitant administration with strong P450 inducers, such as rifampin, are contraindicated since the efficacy of nifedipine tablets could be significantly reduced. (See PRECAUTIONS: Drug Interactions. )

Nifedipine must not be used in cases of cardiogenic shock.

Nifedipine extended-release tablets are contraindicated in patients with a known hypersensitivity to any component of the tablet.

Warnings

Excessive Hypotension

Although in most patients the hypotensive effect of nifedipine is modest and well tolerated, occasional patients have had excessive and poorly tolerated hypotension. These responses have usually occurred during initial titration or at the time of subsequent upward dosage adjustment, and may be more likely in patients using concomitant beta-blockers.

Severe hypotension and/or increased fluid volume requirements have been reported in patients who received immediate-release capsules together with a beta-blocking agent and who underwent coronary artery bypass surgery using high-dose fentanyl anesthesia. The interaction with high-dose fentanyl appears to be due to the combination of nifedipine and a beta-blocker, but the possibility that it may occur with nifedipine alone, with low doses of fentanyl, in other surgical procedures, or with other narcotic analgesics cannot be ruled out. In nifedipine-treated patients where surgery using high-dose fentanyl anesthesia is contemplated, the physician should be aware of these potential problems and, if the patient’s condition permits, sufficient time (at least 36 hours) should be allowed for nifedipine to be washed out of the body prior to surgery.

Increased Angina and/or Myocardial Infarction

Rarely, patients, particularly those who have severe obstructive coronary artery disease, have developed well-documented increased frequency, duration, and/or severity of angina or acute myocardial infarction upon starting nifedipine or at the time of dosage increase. The mechanism of this effect is not established.

Beta-Blocker Withdrawal

When discontinuing a beta-blocker, it is important to taper its dose, if possible, rather than stopping abruptly before beginning nifedipine. Patients recently withdrawn from beta-blockers may develop a withdrawal syndrome with increased angina, probably related to increased sensitivity to catecholamines. Initiation of nifedipine treatment will not prevent this occurrence and on occasion has been reported to increase it.

Congestive Heart Failure

Rarely, patients (usually while receiving a beta-blocker) have developed heart failure after beginning nifedipine. Patients with tight aortic stenosis may be at greater risk for such an event, as the unloading effect of nifedipine would be expected to be of less benefit to these patients, owing to their fixed impedance to flow across the aortic valve.

Precautions

GeneralHypotension

Because nifedipine decreases peripheral vascular resistance, careful monitoring of blood pressure during the initial administration and titration of nifedipine extended-release tablets is suggested. Close observation is especially recommended for patients already taking medications that are known to lower blood pressure (see WARNINGS ).

Peripheral Edema

Mild to moderate peripheral edema occurs in a dose-dependent manner with nifedipine extended-release tablets. The placebo subtracted rate is approximately 8% at 30 mg, 12% at 60 mg and 19% at 90 mg daily. This edema is a localized phenomenon, thought to be associated with vasodilation of dependent arterioles and small blood vessels and not due to left ventricular dysfunction or generalized fluid retention. With patients whose hypertension is complicated by congestive heart failure, care should be taken to differentiate this peripheral edema from the effects of increasing left ventricular dysfunction.

Use in Cirrhotic Patients

Clearance of nifedipine is reduced and systemic exposure increased in patients with cirrhosis. It is unknown how systemic exposure may be altered in patients with moderate or severe liver impairment. Careful monitoring and dose reduction may be necessary; consider initiating therapy with the lowest dose available.

Information for Patients

Nifedipine extended-release tablets are an extended-release tablet and should be swallowed whole and taken on an empty stomach. It should not be administered with food. Do not chew, divide or crush tablets.

Laboratory Tests

Rare, usually transient, but occasionally significant elevations of enzymes such as alkaline phosphatase, CPK, LDH, SGOT and SGPT have been noted. The relationship to nifedipine therapy is uncertain in most cases, but probable in some. These laboratory abnormalities have rarely been associated with clinical symptoms; however, cholestasis with or without jaundice has been reported. A small increase (<5%) in mean alkaline phosphatase was noted in patients treated with nifedipine extended-release tablets. This was an isolated finding and it rarely resulted in values which fell outside the normal range. Rare instances of allergic hepatitis have been reported with nifedipine treatment. In controlled studies, nifedipine extended-release tablets did not adversely affect serum uric acid, glucose, cholesterol or potassium.

Nifedipine, like other calcium channel blockers, decreases platelet aggregation in vitro. Limited clinical studies have demonstrated a moderate but statistically significant decrease in platelet aggregation and increase in bleeding time in some nifedipine patients. This is thought to be a function of inhibition of calcium transport across the platelet membrane. No clinical significance for these findings has been demonstrated.

Positive direct Coombs’ test, with or without hemolytic anemia, has been reported, but a causal relationship between nifedipine administration and positivity of this laboratory test, including hemolysis, could not be determined.

Although nifedipine has been used safely in patients with renal dysfunction and has been reported to exert a beneficial effect in certain cases, rare reversible elevations in BUN and serum creatinine have been reported in patients with pre-existing chronic renal insufficiency. The relationship to nifedipine therapy is uncertain in most cases but probable in some.

Drug Interactions

Nifedipine is mainly eliminated by metabolism and is a substrate of CYP3A. Inhibitors and inducers of CYP3A can impact the exposure to nifedipine and consequently its desirable and undesirable effects. In vitro and in vivo data indicate that nifedipine can inhibit the metabolism of drugs that are substrates of CYP3A, thereby increasing the exposure to other drugs. Nifedipine is a vasodilator, and coadministration of other drugs affecting blood pressure may result in pharmacodynamic interactions.

CYP3A inhibitors such as ketoconazole, fluconazole, itraconazole, clarithromycin, erythromycin (azithromycin, although structurally related to the class of macrolide antibiotic, is void of clinically relevant CYP3A inhibition), grapefruit, nefazodone, fluoxetine, saquinavir, indinavir, nelfinavir, and ritonavir may result in increased exposure to nifedipine when coadministered. Careful monitoring and dose adjustment may be necessary; consider initiating nifedipine at the lowest dose available if given concomitantly with these medications.

Strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, and St. John’s Wort reduce the bioavailability and efficacy of nifedipine; therefore nifedipine should not be used in combination with strong CYP3A inducers such as rifampin (see CONTRAINDICATIONS ).

Antiarrhythmics

Calcium Channel Blockers

ACE Inhibitors

Angiotensin-II Blockers

Beta-Blockers

Nifedipine extended-release tablet was well tolerated when administered in combination with beta-blockers in 187 hypertensive patients in a placebo-controlled clinical trial. However, there have been occasional literature reports suggesting that the combination of nifedipine and beta-adrenergic blocking drugs may increase the likelihood of congestive heart failure, severe hypotension, or exacerbation of angina in patients with cardiovascular disease. Clinical monitoring is recommended, and a dose adjustment of nifedipine should be considered.

Central Alpha1-Blockers

Digitalis

Antithrombotics

Platelet Aggregation Inhibitors

Other

Diuretics, PDE5 inhibitors, alpha-methyldopa: Nifedipine may increase the blood pressure lowering effect of these concomitantly administered agents.

Non-Cardiovascular Drugs

Antifungal Drugs

Ketoconazole, itraconazole and fluconazole are CYP3A inhibitors and can inhibit the metabolism of nifedipine and increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a dose reduction of nifedipine considered.

Antisecretory Drugs

Omeprazole: In healthy volunteers receiving a single dose of 10 mg nifedipine, AUC and C_max of nifedipine after pretreatment with omeprazole 20 mg q.d. for 8 days were 1.26 and 0.87 times those after pretreatment with placebo. Pretreatment with or coadministration of omeprazole did not impact the effect of nifedipine on blood pressure or heart rate. The impact of omeprazole on nifedipine is not likely to be of clinical relevance.

Pantoprazole: In healthy volunteers the exposure to neither drug was changed significantly in the presence of the other drug.

Ranitidine: Five studies in healthy volunteers investigated the impact of multiple ranitidine doses on the single or multiple dose pharmacokinetics of nifedipine. Two studies investigated the impact of coadministered ranitidine on blood pressure in hypertensive subjects on nifedipine. Coadministration of ranitidine did not have relevant effects on the exposure to nifedipine that affected the blood pressure or heart rate in normotensive or hypertensive subjects.

Cimetidine: Five studies in healthy volunteers investigated the impact of multiple cimetidine doses on the single or multiple dose pharmacokinetics of nifedipine. Two studies investigated the impact of coadministered cimetidine on blood pressure in hypertensive subjects on nifedipine. In normotensive subjects receiving single doses of 10 mg or multiple doses of up to 20 mg nifedipine t.i.d. alone or together with cimetidine up to 1000 mg/day, the AUC values of nifedipine in the presence of cimetidine were between 1.52 and 2.01 times those in the absence of cimetidine. The C_max values of nifedipine in the presence of cimetidine were increased by factors ranging between 1.60 and 2.02. The increase in exposure to nifedipine by cimetidine was accompanied by relevant changes in blood pressure or heart rate in normotensive subjects. Hypertensive subjects receiving 10 mg q.d. nifedipine alone or in combination with cimetidine 1000 mg q.d. also experienced relevant changes in blood pressure when cimetidine was added to nifedipine. The interaction between cimetidine and nifedipine is of clinical relevance and blood pressure should be monitored, and a reduction of the dose of nifedipine considered.

Cisapride: Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.

Antibacterial Drugs

Quinupristin/Dalfopristin: In vitro drug interaction studies have demonstrated that quinupristin/dalfopristin significantly inhibits the CYP3A metabolism of nifedipine. Concomitant administration of quinupristin/dalfopristin and nifedipine (repeated oral dose) in healthy volunteers increased AUC and C_max for nifedipine by factors of 1.44 and 1.18, respectively, compared to nifedipine monotherapy. Upon coadministration of quinupristin/dalfopristin with nifedipine, blood pressure should be monitored and a reduction of the dose of nifedipine considered.

Erythromycin: Erythromycin, a CYP3A inhibitor, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a reduction of the dose of nifedipine considered.

Antitubercular Drugs

Rifampin: Strong CYP3A inducers, such as rifampin, rifapentin, and rifabutin reduce the bioavailability of nifedipine which may reduce the efficacy of nifedipine; therefore nifedipine should not be used in combination with strong CYP3A inducers such as rifampin (see CONTRAINDICATIONS ). The impact of multiple oral doses of 600 mg rifampin on the pharmacokinetics of nifedipine after a single oral dose of 20 mg nifedipine capsule was evaluated in a clinical study. Twelve healthy male volunteers received a single oral dose of 20 mg nifedipine capsule on study Day 1. Starting on study Day 2, the subjects received 600 mg rifampin once daily for 14 days. On study Day 15, a second single oral dose of 20 mg nifedipine capsule was administered together with the last dose of rifampin. Compared to study Day 1, 14 days pretreatment with rifampin reduced C_max and AUC of concomitantly administered nifedipine on average by 95% and 97%, respectively.

Antiviral Drugs

Amprenavir, atanazavir, delavirine, fosamprinavir, indinavir, nelfinavir, and ritonavir, as CYP3A inhibitors, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine. Caution is warranted and clinical monitoring of patients recommended.

CNS Drugs

Nefazodone, a CYP3A inhibitor, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a reduction of the dose of nifedipine considered.

Fluoxetine, a CYP3A inhibitor, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a reduction of the dose of nifedipine considered.

Valproic acid may increase the exposure to nifedipine during concomitant therapy. Blood pressure should be monitored and a dose reduction of nifedipine considered.

Phenytoin, Phenobarbital, and Carbamazepine: Nifedipine is metabolized by CYP3A. Coadministration of nifedipine 10 mg capsule and 60 mg nifedipine coat-core tablet with phenytoin, an inducer of CYP3A, lowered the AUC and C_max of nifedipine by approximately 70%. Phenobarbital and carbamazepine are also inducers of CYP3A. Alternative antihypertensive therapy should be considered in patients taking phenytoin, phenobarbital, and carbamazepine.

Antiemetic Drugs

Dolasetron: In patients taking dolasetron by the oral or intravenous route and nifedipine, no effect was shown on the clearance of hydrodolasetron.

Immunosuppressive Drugs

Tacrolimus: Tacrolimus has been shown to be metabolized via the CYP3A system. Nifedipine has been shown to inhibit the metabolism of tacrolimus in vitro. Transplant patients on tacrolimus and nifedipine required from 26% to 38% smaller doses than patients not receiving nifedipine. Nifedipine can increase the exposure to tacrolimus. When nifedipine is coadministered with tacrolimus the blood concentrations of tacrolimus should be monitored and a reduction of the dose of tacrolimus considered.

Sirolimus: A single 60 mg dose of nifedipine and a single 10 mg dose of sirolimus oral solution were administered to 24 healthy volunteers. Clinically significant pharmacokinetic drug interactions were not observed.

Glucose Lowering Drugs

Pioglitazone: Coadministration of pioglitazone for 7 days with 30 mg nifedipine ER administered orally q.d. for 4 days to male and female volunteers resulted in least square mean (90% CI) values for unchanged nifedipine of 0.83 (0.73 to 0.95) for C_max and 0.88 (0.80 to 0.96) for AUC relative to nifedipine monotherapy. In view of the high variability of nifedipine pharmacokinetics, the clinical significance of this finding is unknown.

Rosiglitazone: Coadministration of rosiglitazone (4 mg b.i.d.) was shown to have no clinically relevant effect on the pharmacokinetics of nifedipine.

Metformin: A single dose metformin-nifedipine interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin C_max and AUC by 20% and 9%, respectively, and increased the amount of metformin excreted in urine. T_max and half-life were unaffected. Nifedipine appears to enhance the absorption of metformin.

Miglitol: No effect of miglitol was observed on the pharmacokinetics and pharmacodynamics of nifedipine.

Repaglinide: Coadministration of 10 mg nifedipine with a single dose of 2 mg repaglinide (after 4 days nifedipine 10 mg t.i.d. and repaglinide 2 mg t.i.d.) resulted in unchanged AUC and C_max values for both drugs.

Acarbose: Nifedipine tends to produce hyperglycemia and may lead to loss of glucose control. If nifedipine is coadministered with acarbose, blood glucose levels should be monitored carefully and a dose adjustment of nifedipine considered.

Drugs Interfering with Food Absorption

Orulat: In 17 normal-weight subjects receiving orulat 120 mg t.i.d. for 6 days, orulat did not alter the bioavailability of 60 mg nifedipine (extended-release tablets).

Dietary Supplements

Grapefruit Juice: In healthy volunteers, a single dose coadministration of 250 mL double strength grapefruit juice with 10 mg nifedipine increased AUC and C_max by factors of 1.35 and 1.13, respectively. Ingestion of repeated doses of grapefruit juice (5 × 200 mL in 12 hours) after administration of 20 mg nifedipine ER increased AUC and C_max of nifedipine by a factor of 2. Grapefruit juice should be avoided by patients on nifedipine. The intake of grapefruit juice should be stopped at least 3 days prior to initiating patients on nifedipine.

Herbals

St. John’s Wort: St. John’s Wort is an inducer of CYP3A and may decrease exposure to nifedipine. Alternative antihypertensive therapy should be considered in patients in whom St. John’s Wort therapy is necessary.

CYP2D6 Probe Drug

Debrisoquine: In healthy volunteers, pretreatment with nifedipine 20 mg t.i.d. for 5 days did not change the metabolic ratio of hydroxydebrisoquine to debrisoquine measured in urine after a single dose of 10 mg debrisoquine. Thus, it is improbable that nifedipine inhibits in vivo the metabolism of other drugs that are substrates of CYP2D6.