Moderate Monitor for decreased efficacy of nifedipine if coadministration with brigatinib is necessary. Major Avoid coadministration of nifedipine with carbamazepine and consider alternative therapy if possible. Moderate Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Moderate Nifedipine can have additive hypotensive effects with other antihypertensive agents including carbonic anhydrase inhibitors. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response. 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.
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.
Moderate Monitor for hypotension and other nifedipine-related adverse reactions if coadministration with ceritinib is necessary; a dosage adjustment may be necessary. Inhibitors of CYP3A4 may increase exposure to nifedipine. Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Moderate Cimetidine has been shown to increase the oral bioavailability of dihydropyridines. Cimetidine can potentially affect the disposition of nifedipine due to inhibitory effects on cytochrome P and, therefore, first-pass metabolism of nifedipine, increasing nifedipine bioavailability and serum concentrations.
Lower doses of nifedipine may be considered during concomitant therapy with cimetidine. Moderate Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine. Moderate Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Moderate Fish oil supplements may cause mild, dose-dependent reductions in systolic or diastolic blood pressure in untreated hypertensive patients.
Relatively high doses of fish oil are required to produce any blood pressure lowering effect. Additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. 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.
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 CoQ Coadministration may result in elevated nifedipine plasma concentrations. According to the manufacturer of conivaptan, concomitant use of conivaptan with drugs that are primarily metabolized by CYP3A4, such as nifedipine, should be avoided. Subsequent treatment with CYP3A substrates may be initiated no sooner than 1 week after completion of conivaptan therapy.
Based on the pharmacology of conivaptan, there is potential for additive hypotensive effects when coadministered with calcium-channel blockers. Intravenous infusion of conivaptan has been associated with orthostatic hypotension. Monitor blood pressure and fluid volume status closely in patients receiving conivaptan infusion. Moderate Monitor for an increase in nifedipine-related adverse reactions, including hypotension, if coadministration with crizotinib is necessary.
Moderate Cyclosporine may increase nifedipine blood concentrations when given concomitantly. Concurrent use of cyclosporine and nifedipine has been associated with increased severity and frequency of gingival hyperplasia; patients receiving these drugs together should be instructed to follow strict oral hygiene.
Patients with severe gingival hyperplasia should be promptly referred for evaluation. Nifedipine has been shown to have minimal effects on cyclosporine blood concentrations. Moderate Dalfopristin; quinupristin is a major inhibitor of cytochrome P 3A4 and may decrease the elimination of drugs metabolized by this enzyme including nifedipine.
Moderate Concurrent use with skeletal muscle relaxants and antihypertensive agents may result in additive hypotension. Moderate As darunavir is a CYP3A substrate and inhibitor, interactions with calcium-channel blockers may occur. Nifedipine undergoes significant metabolism via CYP3A4 and increased plasma concentrations would be expected with coadministration.
Cautious dose titration of calcium-channel blockers should be considered; the patient should be monitored for the proper clinical responses to calcium-channel blocker therapy. Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Major According to the manufacturer of nifedipine, coadministration with ritonavir may result in increased exposure to nifedipine, and initiation of nifedipine should begin with the lowest available dose. Anti-retroviral protease inhibitors may decrease the hepatic CYP metabolism of calcium-channel blockers mainly through CYP3A4 inhibition resulting in increased calcium-channel blocker concentrations.
Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval including calcium channel blockers has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted. Moderate Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as nifedipine, should be expected with concurrent use of delavirdine.
Moderate Concomitant administration of dexmedetomidine and calcium-channel blockers could lead to additive hypotension and bradycardia; use together with caution. Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that may lower the heart rate such as calcium-channel blockers. Moderate Dexmethylphenidate can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Periodic evaluation of blood pressure is advisable during concurrent use of dexmethylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of dexmethylphenidate.
Moderate Nifedipine has been reported to rarely decrease quinidine serum concentrations. There have also been reports of no significant change in quinidine concentrations or effect.
In addition, both drugs can cause hypotension, and these effects can be additive. Careful monitoring of serum quinidine concentrations is prudent following the addition or discontinuation of nifedipine, with dose adjustment as clinically warranted. Monitor heart rate, blood pressure, and cardiac response. Moderate Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents.
The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents. Major Diethylpropion has vasopressor effects and may limit the benefit of calcium-channel blockers.
Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. Major Measure serum digoxin concentrations before initiating nifedipine.
This is believed to be due to decreased renal and nonrenal clearance of digoxin by nifedipine. Moderate Diltiazem has been reported to increase the plasma level and hypotensive effects of nifedipine via CYP3A4 inhibition. Major Nifedipine has some potential to reduce cardiac contractility.
Moderate Monitor for an increase in nifedipine-related adverse reactions, including hypotension, if coadministration with dronedarone is necessary. Minor Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients. Drospirenone; Ethinyl Estradiol; Levomefolate: 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. Moderate The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. Moderate Use caution and careful monitoring when coadministering efavirenz with certain calcium-channel blockers. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates e.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: Moderate Administering nifedipine with elbasvir; grazoprevir may result in elevated nifedipine plasma concentrations.
If these drugs are used together, closely monitor for signs of adverse events. Moderate Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents.
Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control. Major The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers.
Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Major Avoid coadministration of nifedipine with enzalutamide, and consider alternative therapy if possible. Major The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers.
Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. Major Close cardiac monitoring is recommended throughout therapy in patients receiving concomitant treatment with epirubicin and calcium-channel blockers. Individuals receiving these medications concurrently are at increased risk of developing heart failure.
Moderate Nifedipine can have additive hypotensive effects with other antihypertensive agents. Moderate Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. Major Because of its potential to cause coronary vasospasm, ergonovine could theoretically antagonize the therapeutic effects of anti-anginal agents including calcium-channel blockers.
In addition, calcium-channel blockers with CYP3A4 inhibitory properties, such as diltiazem, nicardipine, and verapamil, may also reduce the hepatic metabolism of ergonovine and increase the risk of ergot toxicity. Major Avoid administration of erythromycin and a calcium-channel blocker, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock.
Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving calcium-channel blocker therapy. Erythromycin may also decrease the clearance of calcium-channel blockers e. Concurrent use of erythromycin with diltiazem and verapamil has been associated with sudden cardiac death. This interaction is likely due to the combined inhibition of CYP3A by erythromycin and the calcium channel blockers leading to increases in the serum concentrations of erythromycin and the calcium channel blockers.
Minor Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal therapy should be monitored for antihypertensive effectiveness.
Ethinyl Estradiol; Ethynodiol Diacetate: Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: Ethinyl Estradiol; Norethindrone Acetate: Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Ethinyl Estradiol; Norethindrone; Ferrous fumarate: 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. Major Because both flecainide and nifedipine have negative inotropic properties, additive effects are possible especially in patients with abnormal ventricular function.
Per the manufacturer of flecainide, concomitant use with nifedipine is not recommended until more data is available. Moderate Fluconazole may decrease the clearance of calcium-channel blockers, including nifedipine, via inhibition of CYP3A4 metabolism. Consider initiating nifedipine therapy with the lowest available dose if coadminstered with fluconazole. Monitor blood pressure closely during concurrent use of these medications. Moderate Fluoxetine may decrease the clearance of calcium-channel blockers, including nifedipine, via inhibition of CYP3A4 metabolism.
Moderate Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents. Moderate Fosamprenavir may inhibit the metabolism of other medications that are metabolized via CYP3A4. Although drug interaction studies have not been conducted, the serum concentrations of nifedipine may be increased with concomitant administration of fosamprenavir. Moderate Fosphenytoin induces hepatic microsomal enzymes and may increase the metabolism of other drugs, leading to reduced efficacy of the concomitant medication.
When possible, avoid coadministration of these drugs and consider alternative therapy. When an alternative therapy is not possible, patients should be monitored for the desired cardiovascular effects on heart rate, chest pain, or blood pressure. Gallium Ga 68 Dotatate: Moderate Nifedipine can have additive hypotensive effects with other antihypertensive agents including diuretics. Moderate Ginkgo biloba appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme.
More study is needed regarding ginkgo's effects on CYP3A4 and whether clinically significant drug interactions result. Moderate Ginseng appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme.
More study is needed regarding ginseng's effects on CYP3A4 and whether clinically significant drug interactions result. Major Clinicians should be aware that grapefruit juice food interactions with some calcium channel blockers are possible. Grapefruit juice contains compounds psoralen derivatives and possibly the flavonoid naringenin that inhibit the cytochrome P CYP3A4 isozyme in the gut wall. Grapefruit juice can increase the serum concentrations and oral bioavailability of some of the calcium-channel blockers e.
Coadministration of oral nifedipine with grapefruit juice increases the AUC and peak plasma concentrations of nifedipine by 2-fold, with no change in half-life. The increase in nifedipine bioavailability is most likely due to inhibition of the CYP3A4 isoenzyme, resulting in reduced first-pass drug metabolism. To avoid increased drug bioavailability, it is generally recommended to avoid grapefruit juice before or after nifedipine administration.
The manufacturer for Adalat CC recommends stopping grapefruit juice for 3 days prior to initiating nifedipine therapy. Moderate In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. Moderate Hawthorn, Crataegus laevigata also known as C. Following hawthorn administration, the cardiac action potential duration is increased and the refractory period is prolonged.
Hawthorn may also lower peripheral vascular resistance. Patients with hypertension or heart failure should be advised to only use hawthorn with their prescribed medications after discussion with their prescriber. Patients who choose to take hawthorn should receive periodic blood pressure and heart rate monitoring. Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Major Avoid coadministration of nifedipine with idelalisib and consider alternative therapy if possible.
Moderate Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. 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.
Moderate Imatinib is a potent inhibitor of cytochrome P 3A4 and may increase concentrations of other drugs metabolized by this enzyme including nifedipine.
Moderate According to the manufacturer of nifedipine, coadministration with indinavir may result in increased exposure to nifedipine, and initiation of nifedipine should begin with the lowest available dose. Moderate In a study of 9 healthy adults given 0. Moderate Concomitant use of isavuconazonium with nifedipine may result in increased serum concentrations of nifedipine. Nifedipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.
Caution and close monitoring are advised if these drugs are used together. Moderate Additive hypotensive effects may be seen when monoamine oxidase inhibitors MAOIs are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. 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.
Major Avoid coadministration of nifedipine with rifampin, and consider alternative therapy if possible. Moderate The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Moderate Calcium-channel blockers can have a negative inotropic effect that may be additive to those of itraconazole. In addition, itraconazole may increase nifedipine serum concentrations via inhibition of CYP3A4 with the potential for nifedipine toxicity. Edema has been reported in patients receiving concomitantly itraconazole and dihydropyridine calcium-channel blockers; therefore, caution is recommmended when administering these medication in combination.
A dosage reduction of the calcium-channel blocker may be appropriate. Moderate Use caution when administering ivacaftor and nifedipine concurrently.
Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as nifedipine, can increase nifedipine exposure leading to increased or prolonged therapeutic effects and adverse events. Moderate Ketoconazole may decrease the clearance of calcium-channel blockers, such as nifedipine, via inhibition of CYP3A4 metabolism.
Moderate Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as calcium-channel blockers, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenance dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Moderate Concomitant administration of bradycardia-inducing drugs e. Adjust the calcium-channel blocker dose if necessary. Moderate Lesinurad may decrease the systemic exposure and therapeutic efficacy of nifedipine; monitor for potential reduction in efficacy. Moderate Closely monitor for nifedipine-related adverse events if given with letermovir.
In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. A clinically relevant increase in the plasma concentration of nifedipine, a CYP3A4 substrate, may occur during concurrent administration with letermovir, a moderate CYP3A4 inhibitor.
Moderate Levomilnacipran has been associated with an increase in blood pressure. The effectiveness of nifedipine may be diminished during concurrent use of levomilnacipran.
It is advisable to monitor blood pressure if the combination is necessary. Major Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Major Lithium neurotoxicity has been reported during co-administration of lithium and verapamil or diltiazem, and is possible during concurrent use of other calcium-channel blockers with lithium. Symptoms of toxicity have included ataxia, tremors, nausea, vomiting, diarrhea, and tinnitus.
The interaction between verapamil and lithium is variable and unpredictable. Both decreased lithium concentrations and lithium toxicity have been reported after the addition of verapamil. The possibility of a loss of lithium's therapeutic effect due to lower serum lithium concentrations may be offset somewhat by the fact that calcium-channel blocking agents share some neuropharmacological actions with lithium; limited data suggest that oral verapamil is effective in controlling an acute manic episode either as a single agent or in combination with lithium.
Regarding diltiazem, although neurotoxicity was reported after the addition of diltiazem, other drugs were administered concomitantly. Worsened psychosis has been reported with the combination of diltiazem and lithium. Until more data are available, diltiazem and verapamil should be used cautiously in patients receiving lithium. Major Lopinavir; ritonavir Kaletra may decrease the clearance of calcium-channel blockers via inhibition of CYP3A4 metabolism.
Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of lopinavir; ritonavir with other drugs that prolong the PR interval including calcium channel blockers has not been evaluated.
Caution is warranted and clinical monitoring of the patient is recommended. Severe Concomitant use of lumacaftor; ivacaftor and nifedipine is contraindicated because nifedipine's efficacy could be significantly reduced. Nifedipine is primarily metabolized via CYP3A4. Lumacaftor is a strong CYP3A inducer. The impact of strong CYP3A inducers on nifedipine metabolism has been evaluated in clinical studies. Additionally, in vivo data indicate nifedipine may inhibit the metabolism of drugs metabolized via CYP3A, such as ivacaftor; however, this interaction is not likely to be clinically relevant because of the CYP3A induction effects of lumacaftor.
Lumacaftor; ivacaftor dosage adjustments are not recommended with concomitant use of a moderate CYP3A inhibitor such as nifedipine. 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.
Major Clinically significant drug interactions including neuromuscular blockade and hypotension have occurred when IV magnesium salts were given concurrently with nifedipine during the treatment of hypertension or premature labor during pregnancy.
The effects have been attributed to nifedipine potentiation of the neuromuscular blocking effects of magnesium. It is recommended that nifedipine not be given concurrently with magnesium therapy for pre-eclampsia, hypertension, or tocolytic treatment during pregnancy.
Minor Use caution and careful monitoring with the coadministration of maraviroc and nifedipine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein Pgp ; nifedipine is a mild inhibitor of Pgp.
The effects of Pgp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible. Moderate Melatonin may impair the efficacy of some calcium-channel blockers, and caution is advised with concurrent use. In one placebo-controlled study, melatonin evening ingestion led to significant increases in blood pressure 6.
Melatonin appeared to antagonize the antihypertensive effects of nifedipine. The mechanism of this interaction is unclear. It may be prudent to avoid melatonin use during calcium-channel blocker therapy. Minor Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients; monitor patients receiving concurrent therapy to confirm that the desired antihypertensive effect is being obtained.
Major Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium channel blockers. Minor Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Moderate Methylphenidate can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate.
Major Because of the potential to cause coronary vasospasm , methysergide theoretically could antagonize the therapeutic effects of calcium-channel blockers. Clinicians should also note that calcium-channel blockers with CYP3A4 inhibitory properties, such as diltiazem, nicardipine, verapamil, may also reduce the hepatic metabolism of selected ergot alkaloids and increase the risk of ergot toxicity.
Moderate Concomitant nifedipine and micafungin administration may increase the systemic exposure and the maximum serum concentration of nifedipine.
Patients should be monitored closely for nifedipine-related side effects; nifedipine dosage reduction may be necessary. Moderate Mifepristone inhibits CYP3A4 and coadministration of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates, including many of the calcium-channel blockers.
Drugs in which CYP3A is the primary route of metabolism should be used with caution if co-administered with mifepristone. For calcium channel blockers, monitor blood pressure, heart rate, fluid retention and for shortness of breath as potential side effects.
Avoiding calcium channel blockers by using other classes of antihypertensive agents that are not substrates for CYP3A4 may be appropriate in some patients requiring long-term administration of inhibitory drugs. Moderate Milnacipran has been associated with an increase in blood pressure.
The effectiveness of antihypertensive agents may be diminished during concurrent use of milnacipran. Digital anomalies have been reported to occur with other members of the dihydropyridine class and are possibly a result of compromised uterine blood flow.
There are no adequate and well-controlled studies in pregnant women. Lactation Nifedipine is transferred through breast milk. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Age appears to have a significant effect on the pharmacokinetics of nifedipine. The clearance is decreased resulting in a higher AUC in the elderly. Generally, overdosage with nifedipine leading to pronounced hypotension calls for active cardiovascular support, including monitoring of cardiovascular and respiratory function, elevation of extremities, judicious use of calcium infusion, pressor agents, and fluids.
Clearance of nifedipine would be expected to be prolonged in patients with impaired liver function. Since nifedipine is highly protein-bound, dialysis is not likely to be of any benefit. The main effects of ingestion of approximately mg of PROCARDIA XL in a young man attempting suicide as a result of cocaine -induced depression was initial dizziness, palpitations , flushing, and nervousness.
Within several hours of ingestion, nausea, vomiting, and generalized edema developed. No significant hypotension was apparent at presentation, 18 hours post-ingestion. Vital signs remained stable, no electrocardiographic abnormalities were noted, and renal function returned to normal within 24 to 48 hours with routine supportive measures alone.
No prolonged sequelae were observed. The effect of a single mg ingestion of PROCARDIA capsules in a depressed anginal patient also on tricyclic antidepressants was loss of consciousness within 30 minutes of ingestion, and profound hypotension, which responded to calcium infusion, pressor agents, and fluid replacement. A variety of ECG abnormalities were seen in this patient with a history of bundle branch block, including sinus bradycardia and varying degrees of AV block.
These dictated the prophylactic placement of a temporary ventricular pacemaker , but otherwise resolved spontaneously. Significant hyperglycemia was seen initially in this patient, but plasma glucose levels rapidly normalized without further treatment. A young hypertensive patient with advanced renal failure ingested mg of PROCARDIA capsules at one time, with resulting marked hypotension responding to calcium infusion and fluids. No AV conduction abnormalities, arrhythmias, or pronounced changes in heart rate were noted, nor was there any further deterioration in renal function.
The contractile processes of cardiac muscle and vascular smooth 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 cardiac muscle and vascular smooth muscle without altering serum calcium concentrations. Mechanism of Action Angina The precise mechanisms by which inhibition of calcium influx relieves angina has not been fully determined, but includes at least the following two mechanisms: Relaxation and Prevention of Coronary Artery Spasm Nifedipine dilates the main coronary arteries and coronary arterioles, both in normal and ischemic regions, and is a potent inhibitor of coronary artery spasm , whether spontaneous or ergonovine-induced.
This property increases myocardial oxygen delivery in patients with coronary artery spasm, and is responsible for the effectiveness of nifedipine in vasospastic Prinzmetal's or variant angina. Whether this effect plays any role in classical angina is not clear, but studies of exercise tolerance have not shown an increase in the maximum exercise rate-pressure product, a widely accepted measure of oxygen utilization.
This suggests that, in general, relief of spasm or dilation of coronary arteries is not an important factor in classical angina. Reduction of Oxygen Utilization Nifedipine regularly reduces arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing the total peripheral vascular resistance afterload against which the heart works. This unloading of the heart reduces myocardial energy consumption and oxygen requirements, and probably accounts for the effectiveness of nifedipine in chronic stable angina.
Hypertension The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and the resulting reduction in peripheral vascular resistance. The increased peripheral vascular resistance that is 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. For subsequent doses, relatively constant plasma concentrations at this plateau are maintained with minimal fluctuations over the hour dosing interval. Markedly reduced gastrointestinal retention time over prolonged periods i. There was no evidence of dose dumping either in the presence or absence of food for over subjects in pharmacokinetic studies.
The elimination half-life of nifedipine is approximately two hours. Only traces less than 0. The remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion.
Thus, the pharmacokinetics of nifedipine are not significantly influenced by the degree of renal impairment. Patients in hemodialysis or chronic ambulatory peritoneal dialysis have not reported significantly altered pharmacokinetics of nifedipine.
Since hepatic biotransformation is the predominant route for the disposition of nifedipine, the pharmacokinetics may be altered in patients with chronic liver disease. Patients with hepatic impairment liver cirrhosis have a longer disposition half-life and higher bioavailability of nifedipine than healthy volunteers.
Protein binding may be greatly reduced in patients with renal or hepatic impairment. 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—10 mm Hg systolic , but sometimes larger.
Hemodynamic studies 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 has had no tendency to prolong atrioventricular conduction or sinus node recovery time, or to slow sinus rate.
Do not chew, divide or crush tablets. Do not be concerned if you occasionally notice in your stool something that looks like a tablet. When this process is completed, the empty tablet is eliminated from your body.
Moderate Monitor for adverse effects if silodosin is coadministered with nifedipine. Half life hydrocodone urine Coadministration of clarithromycin and calcium-channel blockers should be avoided if daily, maximum in dose patients, due to an increased risk of hypotension and acute kidney injury. If used concurrently, close clinical monitoring with appropriate reductions are advised. Ivacaftor is an inhibitor of CYP3A. Concurrent use of erythromycin with diltiazem and verapamil has been associated dose sudden cardiac death. Moderate Milnacipran has been associated with an increase in blood procardia. Moderate Fluconazole may decrease the clearance of calcium-channel blockers, including nifedipine, via inhibition of CYP3A4 metabolism. Although nifedipine has been daily 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 preexisting maximum renal insufficiency. More study is needed regarding ginkgo's effects on CYP3A4 and whether procardia daily drug interactions result. Nifedipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Major Nifedipine has some potential to reduce cardiac contractility. Moderate According to the manufacturer of nifedipine, coadministration with indinavir procardia result in increased exposure to nifedipine, and initiation of nifedipine should begin with the lowest available dose. Hawthorn may also lower peripheral vascular resistance. Blood pressure and heart rates should be monitored closely to confirm that the desired dose effect is achieved. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. In an uncontrolled study of over two hundred patients with congestive heart failure during which digoxin blood levels were not measured, maximum daily dose procardia xl, digitalis toxicity was not observed. Patients with tight aortic stenosis may be at greater risk for such an event, as the unloading effect of nifedipine would be maximum to be of less benefit, owing to the fixed impedance to flow across the aortic valve in these patients, maximum daily dose procardia xl.
Moderate According to the manufacturer of nifedipine, coadministration with indinavir may result in increased exposure to nifedipine, and initiation of nifedipine should begin with the lowest available dose. 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. Monitor blood pressure if the combination is necessary. Patients with tight aortic stenosis may be at maximum dose for such an event, as the unloading effect of nifedipine would be expected to be of less benefit, owing procardia the fixed impedance to flow across the aortic valve in these patients. Moderate Fosamprenavir may inhibit the metabolism of other medications that are metabolized via CYP3A4. Individuals daily these medications concurrently are at increased risk of developing heart failure, maximum daily dose procardia xl. The clearance is decreased resulting in a higher AUC in the elderly. Moderate Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Consider the benefits of breast-feeding, the risk of potential infant drug exposure, maximum daily dose procardia xl, and the risk of an untreated or inadequately treated condition.
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