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Adalat CC
Classes
Dihydropyridine Calcium Channel Blockers
Administration
If gastric irritation becomes problematic, administer oral doses with meals. According to the manufacturer, Adalat CC should be administered on an empty stomach.
Avoid grapefruit juice before or after drug administration to avoid potential increases in nifedipine bioavailability.
Nifedipine immediate-release capsules and sustained-release tablets should be swallowed whole. Do not crush, break, or chew sustained-release tablets. Advise patient that empty tablet shells in the stool are not significant.
Two 30 mg Adalat CC tablets may be interchanged with a 60 mg Adalat CC tablet. However, three 30 mg tablets will result in a substantially higher Cmax than a single 90 mg Adalat CC tablet. Therefore, three 30 mg tablets should not be considered interchangeable with a 90 mg tablet.
NOTE: Nifedipine rectal ointment is not approved by the FDA for rectal topical administration.
Extemporaneous compounding instructions for Nifedipine 0.5% rectal topical ointment
Dilute 100 mg of nifedipine in 20 grams of yellow soft paraffin (yellow petroleum jelly). White petrolatum has also been used as a compounding base.
Mix, using a spatula, to form a uniform smooth preparation.
The formula remains stable for approximately 1 year when stored at room temperature at 25 degrees C (77 degrees F) and in white opaque polypropylene containers.
Sublingual Administration†
Not recommended. There is no difference in relative bioavailability when immediate-release capsules are administered whole, bitten and swallowed, or bitten and held sublingually. Sublingual administration offers no advantage over oral administration of the immediate-release capsules.
Adverse Reactions
heart failure / Delayed / 2.0-6.7
myocardial infarction / Delayed / 4.0-6.7
atrial fibrillation / Early / 0-1.0
arrhythmia exacerbation / Early / 0-1.0
cardiac arrest / Early / 0-1.0
bradycardia / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
GI bleeding / Delayed / 0-1.0
ocular hemorrhage / Delayed / 0-1.0
visual impairment / Early / 0-1.0
exfoliative dermatitis / Delayed / 0-0.5
Stevens-Johnson syndrome / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known
bezoar / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
peripheral edema / Delayed / 4.0-30.0
palpitations / Early / 0-7.0
wheezing / Rapid / 6.0-6.0
dyspnea / Early / 0-6.0
hypotension / Rapid / 0-5.0
constipation / Delayed / 0-3.3
chest pain (unspecified) / Early / 0-3.0
impotence (erectile dysfunction) / Delayed / 0-3.0
blurred vision / Early / 0-2.0
angina / Early / 0-1.0
phlebitis / Rapid / 0-1.0
orthostatic hypotension / Delayed / 0-1.0
premature ventricular contractions (PVCs) / Early / 0-1.0
sinus tachycardia / Rapid / 0-1.0
hypertonia / Delayed / 0-1.0
ataxia / Delayed / 0-1.0
confusion / Early / 0-1.0
depression / Delayed / 0-1.0
migraine / Early / 0-1.0
gingival hyperplasia / Delayed / 0-1.0
dysphagia / Delayed / 0-1.0
esophagitis / Delayed / 0-1.0
melena / Delayed / 0-1.0
dysuria / Early / 0-1.0
nephrolithiasis / Delayed / 0-1.0
hematuria / Delayed / 0-1.0
gout / Delayed / 0-1.0
myasthenia / Delayed / 0-1.0
amblyopia / Delayed / 0-1.0
conjunctivitis / Delayed / 0-1.0
eosinophilia / Delayed / 0-1.0
lymphadenopathy / Delayed / 0-1.0
hot flashes / Early / 0-1.0
leukopenia / Delayed / 0-0.5
thrombocytopenia / Delayed / 0-0.5
anemia / Delayed / 0-0.5
peripheral vasodilation / Rapid / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
dizziness / Early / 4.0-27.0
flushing / Rapid / 0-25.0
headache / Early / 10.0-23.0
weakness / Early / 10.0-12.0
nausea / Early / 2.0-11.0
pyrosis (heartburn) / Early / 11.0-11.0
tremor / Early / 0-8.0
muscle cramps / Delayed / 0-8.0
throat irritation / Early / 6.0-6.0
cough / Delayed / 0-6.0
nasal congestion / Early / 0-6.0
fatigue / Early / 4.0-5.9
asthenia / Delayed / 0-4.0
vertigo / Early / 0-3.0
drowsiness / Early / 0-3.0
paresthesias / Delayed / 0-3.0
insomnia / Early / 0-3.0
epistaxis / Delayed / 0-3.0
rhinitis / Early / 0-3.0
rash / Early / 0-3.0
pruritus / Rapid / 0-3.0
xerostomia / Early / 0-3.0
abdominal pain / Early / 0-3.0
diarrhea / Early / 0-3.0
dyspepsia / Early / 0-3.0
flatulence / Early / 0-3.0
increased urinary frequency / Early / 0-3.0
polyuria / Early / 0-3.0
arthralgia / Delayed / 0-3.0
urticaria / Rapid / 0-2.0
hyperhidrosis / Delayed / 0-2.0
chills / Rapid / 0-2.0
fever / Early / 0-2.0
syncope / Early / 0-1.0
libido decrease / Delayed / 0-1.0
hypoesthesia / Delayed / 0-1.0
nightmares / Early / 0-1.0
anxiety / Delayed / 0-1.0
pharyngitis / Delayed / 0-1.0
sinusitis / Delayed / 0-1.0
petechiae / Delayed / 0-1.0
photosensitivity / Delayed / 0-1.0
purpura / Delayed / 0-1.0
alopecia / Delayed / 0-1.0
gynecomastia / Delayed / 0-1.0
breast enlargement / Delayed / 0-1.0
mastalgia / Delayed / 0-1.0
gastroesophageal reflux / Delayed / 0-1.0
weight gain / Delayed / 0-1.0
weight loss / Delayed / 0-1.0
vomiting / Early / 0-1.0
dysgeusia / Early / 0-1.0
eructation / Early / 0-1.0
pelvic pain / Delayed / 0-1.0
nocturia / Early / 0-1.0
myalgia / Early / 0-1.0
back pain / Delayed / 0-1.0
diplopia / Early / 0-1.0
lacrimation / Early / 0-1.0
tinnitus / Delayed / 0-1.0
malaise / Early / 0-1.0
paranoia / Early / 0-0.5
Common Brand Names
Adalat, Adalat CC, Afeditab CR, Nifediac CC, Nifedical XL, Procardia, Procardia XL
Dea Class
Rx
Description
Oral calcium-channel blocker; prototype dihydropyridine with more prominent effects on vasodilation and coronary flow than diltiazem and verapamil; lacks effects on AV conduction; primarily used for angina, Prinzmetal's angina, and HTN.
Dosage And Indications
10 mg PO 3 times daily, initially. Increase the dose every 7 to 14 days until desired clinical response is achieved. May increase dose to 20 mg PO 3 times daily, then 30 mg PO 3 times daily over 3 days if needed or may increase dose by 10 mg/dose every 4 to 6 hours for hospitalized patients. Usual dose: 10 to 20 mg PO 3 times daily. Usual Max: 30 mg/dose and 120 mg/day. Max: 180 mg/day.
30 or 60 mg PO once daily, initially. Increase the dose every 7 to 14 days until desired clinical response is achieved. Usual Max: 90 mg/day. Max: 120 mg/day.
0.2 to 0.5 mg/kg/dose (Max: 10 mg/dose) PO every 4 to 6 hours as needed. To avoid a precipitous and unexpected drop in blood pressure, some authors recommend initial doses less than 0.2 mg/kg and avoiding use in patients with CNS injury. Mean doses of 0.22 to 0.23 mg/kg (range: 0.04 to 0.69 mg/kg) have been reported in retrospective studies (n = 299 pediatric patients 0.1 to 18.9 years). NOTE: Per the FDA and manufacturers, immediate-release nifedipine dosage forms should not be used to treat hypertension and should only be used to treat patients with chronic stable angina or vasospastic angina. The immediate-release nifedipine formulation has been associated with serious side effects when used to treat adult patients with hypertension, hypertensive urgency, hypertensive emergency, or coexisting myocardial infarction. Although the use of immediate-release nifedipine for the treatment acute hypertensive episodes is still relatively common practice in pediatric patients, considerable controversy exists and caution should be used.
30 or 60 mg PO once daily, initially. May increase dose over 7 to 14 days if further control is needed. Usual dose range: 30 to 90 mg/day. Max: 120 mg/day.
0.2 to 0.5 mg/kg/day PO in 1 to 2 divided doses. May increase dose if further control is needed. Max: 3 mg/kg/day. A maximum of 120 mg/day PO has been recommended by pediatric hypertension guidelines; however, some experts recommend that doses up to 180 mg/day may be necessary in some clinical situations. Extended-release tablets must be swallowed whole and are too large for young children.
Conflicting data exist regarding the use of nifedipine for proteinuria associated with diabetic nephropathy. A significant increase in urinary albumin excretion was reported in 7 normotensive patients with diabetic nephropathy who were treated with slow-release nifedipine 20 mg PO twice daily and followed for 6 weeks. A significant increase in urinary albumin excretion was also reported in a crossover study of 14 non-insulin dependent diabetic patients during a 20-week trial. The mean study dose was 45 +/- 8 mg of long-acting nifedipine once daily. Conversely, in another study, 27 diabetics with persistent microalbuminuria received nifedipine 20 to 80 mg PO once daily for 12 months. These data demonstrated a decrease in urinary albumin excretion (UAE) during therapy, however, UAE increased to levels greater than baseline once therapy was discontinued.
See adult dosage. In general, initiate dosage at the lower end of the adult dosage range. Nifedipine plasma concentrations and half-life are significantly increased in geriatric patients. Adjust dosage based on clinical response.
Doses of 10 to 20 mg PO 3 times daily have been used.
See adult dosage. In general, initiate dosage at the lower end of the adult dosage range. Nifedipine plasma concentrations and half-life are significantly increased in geriatric patients. Adjust dosage based on clinical response.
NOTE: Clinical practice guidelines recommend the use of a first line tocolytic (i.e., beta agonist, calcium channel blocker, or NSAID) for short-term use (up to 48 hours) to allow for administration of antenatal corticosteroids to enhance fetal lung maturation, magnesium sulfate for fetal neuroprotection, or transport to a tertiary facility, if indicated. There is no evidence that tocolytic therapy alone has any favorable effect on neonatal outcomes. Maintenance therapy with tocolytics is ineffective for preventing preterm birth and improving neonatal outcomes and is not recommended.
Oral dosage - immediate-release (Procardia) Pregnant females
Various regimens have been used. The recommended dose by the American College of Obstetrics and Gynecology (ACOG) is a 30-mg loading dose, followed by 10 to 20 mg every 4 to 6 hours. NOTE: A route of administration is not provided, although typically PO and/or SL is used for the loading dose and PO is used for subsequent dosing. Typical regimens for the loading dose include 10 mg SL with 20 mg PO, 30 mg PO, or 10 to 20 mg SL or PO every 15 to 20 minutes until contractions stop, up to a maximum of 30 to 40 mg over 1 hour. Although not definitive, typical duration of tocolysis for acute inhibition of premature labor is 24 to 72 hours. When compared to ritodrine or magnesium sulfate, nifedipine has generally demonstrated similar efficacy with similar or fewer maternal side effects. Although maintenance use of tocolytics after acute suppression of contractions has not been shown to prolong pregnancy, doses of 10 to 20 mg PO every 4 to 6 hours have been used. Additionally, some studies have used maintenance dosing with slow-release nifedipine (doses of 60 to 160 mg/day PO). Magnesium sulfate therapy should not be given concurrently because of additive effects on maternal cardiac function.
10 to 30 mg PO, 30 to 45 minutes before meals, has been used. Nifedipine inhibits lower esophageal (LES) muscle contraction by blocking cellular calcium uptake and lowers the LES resting pressure by 30% to 60%; side effects (e.g., hypotension, headache, pedal edema) and tolerance may limit its utility. Reserve for patients who refuse or are not candidates for more definitive therapies (pneumatic dilation or surgical myotomy) or who fail to respond to botulinum toxin injections.
0.5 mg/kg/dose (Max: 20 mg/dose) PO every 8 hours until symptoms resolve. May consider further use if resuming ascent. Nifedipine is suggested in the rare case where response to oxygen and/or descent is unsatisfactory. The extended-release formulation is preferred over immediate-release.
30 mg PO every 12 hours or 20 mg PO every 8 hours until symptoms resolve. Nifedipine is suggested as an adjunct to descent, oxygen, or portable hyperbaric therapy in the field setting where resources are limited; it may be used as primary therapy if these measures are not feasible.
0.5 mg/kg/dose (Max: 40 mg/dose) PO every 8 hours until symptoms resolve. May consider further use if resuming ascent. Nifedipine is suggested in the rare case where response to oxygen and/or descent is unsatisfactory.
30 mg PO every 12 hours or 20 mg PO every 8 hours starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated. Prophylactic medications should only be considered for individuals with a prior history of high altitude pulmonary edema.
20 mg PO twice daily for 6 to 8 weeks. Guidelines suggest topical calcium channel blockers as first-line therapy. Given the higher incidence of adverse effects with oral calcium channel blockers, topical administration is preferred.
Apply an almond-sized amount intra-anally every 8 to 12 hours for 2 to 8 weeks. Guidelines suggest topical calcium channel blockers as first-line therapy.
30 mg PO once daily, initially. Increase the dose to 60 to 120 mg PO twice daily as tolerated.
0.3 to 0.6 mg/kg/dose PO once daily, initially. Increase dose as tolerated. Usual dose: 2 to 3 mg/kg/day. Max: 180 mg/day.
10 mg PO 3 times daily for 2 to 7 days, then 20 mg PO 3 times daily for up 8 to 12 weeks.
†Indicates off-label use
Dosing Considerations
Dosage reduction and close monitoring of blood pressure is advised in patients with hepatic impairment. Although no specific guidelines are available, the half-life and AUC of nifedipine is markedly increased in cirrhotic patients.
Renal ImpairmentNo dosage adjustment is needed.
Intermittent hemodialysis
Nifedipine is minimally removed by hemodialysis or hemoperfusion. Therefore, no supplemental dosage is needed following hemodialysis.
Drug Interactions
Acebutolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Ibuprofen: (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.
Acetaminophen; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Adagrasib: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with adagrasib as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor.
Adenosine: (Moderate) Use adenosine with caution in the presence of calcium-channel blockers due to the potential for additive or synergistic depressant effects on the sinoatrial and atrioventricular nodes.
Aldesleukin, IL-2: (Moderate) Calcium channel blockers 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.
Alfentanil: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with nifedipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving nifedipine.
Alfuzosin: (Moderate) The concomitant administration of alpha-blockers with other antihypertensive agents can cause additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Alogliptin; Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Alogliptin; Pioglitazone: (Minor) Concentrations of nifedipine may be decreased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of nifedipine ER was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with nifedipine ER 30 mg once daily for 4 days resulted in a 13% and 17% reduction in nifedipine ER AUC and Cmax, respectively. In addition, coadministration for 7 days resulted in a 5% and 4% increase in pioglitazone AUC and Cmax, respectively. Patients should be monitored for the desired cardiovascular effects on heart rate, chest pain, or blood pressure; nifedipine dosages may need to be adjusted while the patient is receiving pioglitazone. Close monitoring of blood glucose is also recommended; dosage adjustments in pioglitazone may be needed.
Alprazolam: (Moderate) In patients taking drugs that inhibit CYP3A isoenzymes, use alprazolam with caution and consider alprazolam dose reduction (up to 50% dose reduction may be needed). Niifedipine may theoretically inhibit CYP3A4 metabolism of alprazolam.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, like calcium channel blockers, 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.
Amifostine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Aminolevulinic Acid: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Amiodarone: (Moderate) Amiodarone is a CYP3A4 inhibitor, which theoretically may decrease hepatic clearance and enhance oral bioavailability of nifedipine (CYP3A4 substrate).
Amlodipine; Celecoxib: (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.
Amobarbital: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin and nifedipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving nifedipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Nifedipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Apalutamide: (Major) Avoid coadministration of nifedipine with apalutamide and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Apomorphine: (Moderate) Use of calcium-channel blockers and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Apraclonidine had minimal effects on heart rate and blood pressure during clinical studies in patients with glaucoma. However, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Use caution during concurrent use, especially in patients with severe, uncontrolled cardiovascular disease, including hypertension.
Aprepitant, Fosaprepitant: (Moderate) Use caution if nifedipine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in nifedipine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Nifedipine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of nifedipine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Articaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
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.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Atazanavir: (Moderate) Atazanavir may interact with certain calcium-channel blockers that undergo significant metabolism via CYP3A4, including nifedipine. Cautious dose titration of amlodipine should be considered; the patient should be monitored for the proper clinical responses to calcium-channel blocker therapy.
Atazanavir; Cobicistat: (Moderate) Atazanavir may interact with certain calcium-channel blockers that undergo significant metabolism via CYP3A4, including nifedipine. Cautious dose titration of amlodipine should be considered; the patient should be monitored for the proper clinical responses to calcium-channel blocker therapy. (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as nifedipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
Atenolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Atenolol; Chlorthalidone: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Avanafil: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response. For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
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.
Barbiturates: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Benzphetamine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Berotralstat: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with berotralstat as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; berotralstat is a moderate CYP3A4 inhibitor.
Beta-blockers: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Betaxolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Bisoprolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
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.
Bosentan: (Moderate) Closely monitor blood pressure if coadministration of nifedipine with bosentan is necessary; decreased plasma concentrations of nifedipine may occur. Nifedipine is a CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer.
Brimonidine; Timolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Bupivacaine; Meloxicam: (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.
Butabarbital: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Butalbital; Acetaminophen: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including nifedipine. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Canagliflozin; Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Carbamazepine: (Major) Avoid coadministration of nifedipine with carbamazepine and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and carbamazepine is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
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.
Carbonic anhydrase inhibitors: (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.
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.
Carteolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Carvedilol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Celecoxib: (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.
Celecoxib; Tramadol: (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.
Ceritinib: (Moderate) Monitor blood pressure if coadministration of nifedipine with ceritinib is necessary; consider decreasing the dose of nifedipine if appropriate. Nifedipine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Concomitant use may increase nifedipine exposure.
Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (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) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Cimetidine: (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-450 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.
Cisapride: (Moderate) Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.
Clarithromycin: (Major) Avoid coadministration of clarithromycin and nifedipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving nifedipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Nifedipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
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.
Cobicistat: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as nifedipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
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; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Codeine; Phenylephrine; Promethazine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
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.
Conivaptan: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with conivaptan as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an increase in nifedipine-related adverse reactions, including hypotension, if coadministration with crizotinib is necessary. Nifedipine is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (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.
Danazol: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Dantrolene: (Moderate) Concurrent use with skeletal muscle relaxants and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Dapagliflozin; Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Darunavir: (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: (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. (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as nifedipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (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. (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as nifedipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
Delavirdine: (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.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dexmedetomidine: (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.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dextromethorphan; Quinidine: (Moderate) Nifedipine has been reported to rarely decrease quinidine serum concentrations. Quinidine concentrations may decrease by 20% to 40% when nifedipine is added, and potentially increase after nifedipine is withdrawn. 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.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
Diclofenac: (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.
Diclofenac; Misoprostol: (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.
Diethylpropion: (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.
Diflunisal: (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.
Digoxin: (Major) Measure serum digoxin concentrations before initiating nifedipine. If necessary, reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Coadministration of digoxin and nifedipine increases the serum concentration of digoxin by 45%. This is believed to be due to decreased renal and nonrenal clearance of digoxin by nifedipine.
Diltiazem: (Moderate) Diltiazem has been reported to increase the plasma level and hypotensive effects of nifedipine via CYP3A4 inhibition.
Diphenhydramine; Ibuprofen: (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.
Diphenhydramine; Naproxen: (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-depen
Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Disopyramide: (Major) Nifedipine has some potential to reduce cardiac contractility. Use caution when administering concomitantly with other agents known to affect cardiac contractility and/or conduction such as disopyramide.
Dorzolamide; Timolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Dronedarone: (Moderate) Monitor for an increase in nifedipine-related adverse reactions, including hypotension, if coadministration with dronedarone is necessary. Nifedipine is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
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.
Dutasteride; Tamsulosin: (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. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Efavirenz: (Moderate) Use caution and careful monitoring when coadministering efavirenz with certain calcium-channel blockers. Efavirenz induces CYP3A4, potentially altering serum concentrations of calcium-channel blockers metabolized via CYP3A4. When coadministered, efavirenz decreases the concentrations of diltiazem (decrease in Cmax by 60%, in AUC by 69%, and in Cmin by 63%) and its active metabolites, desacetyl diltiazem and N-monodesmethyl diltiazem; dose adjustments are made based on clinical response. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates (e.g., felodipine, lercanidipine, nicardipine, and verapamil); adjust based on clinical response.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use caution and careful monitoring when coadministering efavirenz with certain calcium-channel blockers. Efavirenz induces CYP3A4, potentially altering serum concentrations of calcium-channel blockers metabolized via CYP3A4. When coadministered, efavirenz decreases the concentrations of diltiazem (decrease in Cmax by 60%, in AUC by 69%, and in Cmin by 63%) and its active metabolites, desacetyl diltiazem and N-monodesmethyl diltiazem; dose adjustments are made based on clinical response. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates (e.g., felodipine, lercanidipine, nicardipine, and verapamil); adjust based on clinical response.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Use caution and careful monitoring when coadministering efavirenz with certain calcium-channel blockers. Efavirenz induces CYP3A4, potentially altering serum concentrations of calcium-channel blockers metabolized via CYP3A4. When coadministered, efavirenz decreases the concentrations of diltiazem (decrease in Cmax by 60%, in AUC by 69%, and in Cmin by 63%) and its active metabolites, desacetyl diltiazem and N-monodesmethyl diltiazem; dose adjustments are made based on clinical response. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates (e.g., felodipine, lercanidipine, nicardipine, and verapamil); adjust based on clinical response.
Elbasvir; Grazoprevir: (Moderate) Administering nifedipine with elbasvir; grazoprevir may result in elevated nifedipine plasma concentrations. Nifedipine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as nifedipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as nifedipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
Empagliflozin: (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.
Empagliflozin; Linagliptin: (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.
Empagliflozin; Linagliptin; Metformin: (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. (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Empagliflozin; Metformin: (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. (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Enzalutamide: (Major) Avoid coadministration of nifedipine with enzalutamide, and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and enzalutamide is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Ephedrine: (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.
Ephedrine; Guaifenesin: (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.
Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Epirubicin: (Moderate) Close cardiac monitoring is recommended throughout therapy in patients receiving concomitant therapy with epirubicin and calcium-channel blockers. Individuals receiving these medications together are at increased risk of developing heart failure.
Eplerenone: (Moderate) Nifedipine can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Epoprostenol: (Moderate) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Ertugliflozin; Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Erythromycin: (Major) Avoid administration of erythromycin and nifedipine, 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 nifedipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Nifedipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Esmolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Estradiol: (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; Norelgestromin: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Etodolac: (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.
Etomidate: (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.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Fedratinib: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with fedratinib as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; fedratinib is a moderate CYP3A4 inhibitor.
Fenoprofen: (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.
Fentanyl: (Moderate) Severe hypotension and/or increased fluid volume requirements have been reported in patients receiving nifedipine together with a beta-blocking agent 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.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Finasteride; Tadalafil: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response. For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
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.
Flecainide: (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.
Fluconazole: (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.
Fluoxetine: (Moderate) Fluoxetine may decrease the clearance of calcium-channel blockers, including nifedipine, via inhibition of CYP3A4 metabolism.
Flurbiprofen: (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.
Fosamprenavir: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with fosamprenavir as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Major) Avoid coadministration of nifedipine with fosphenytoin and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
General anesthetics: (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.
Ginkgo, Ginkgo biloba: (Moderate) Ginkgo biloba appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginkgo with nifedipine resulted in a 53% increase in nifedipine peak concentrations. More study is needed regarding ginkgo's effects on CYP3A4 and whether clinically significant drug interactions result.
Ginseng, Panax ginseng: (Moderate) Ginseng appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginseng with nifedipine resulted in a 30% increase in nifedipine peak concentrations. More study is needed regarding ginseng's effects on CYP3A4 and whether clinically significant drug interactions result.
Glipizide; Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Glyburide; Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Grapefruit juice: (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-450 CYP3A4 isozyme in the gut wall. Grapefruit juice can increase the serum concentrations and oral bioavailability of some of the calcium-channel blockers (e.g., felodipine, nicardipine, nifedipine, nimodipine, nisoldipine, and verapamil); no significant effect on diltiazem bioavailability has been reported. 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.
Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Haloperidol: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Hydrocodone; Ibuprofen: (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.
Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Ibuprofen: (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.
Ibuprofen; Famotidine: (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.
Ibuprofen; Oxycodone: (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.
Ibuprofen; Pseudoephedrine: (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) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Idelalisib: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with idelalisib as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor.
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) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Imatinib: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including nifedipine.
Indinavir: (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. 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. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Indocyanine Green: (Moderate) In a study of 9 healthy adults given 0.5 mg/kg of indocyanine green, nifedipine increased indocyanine green clearance by 14%.
Indomethacin: (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.
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.
Isavuconazonium: (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.
Isocarboxazid: (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.
Isoflurane: (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.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of nifedipine with rifampin, and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and rifampin is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of nifedipine with rifampin, and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and rifampin is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Isoproterenol: (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.
Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Isosorbide Mononitrate: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Itraconazole: (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 recommended when administering these medication in combination. A dosage reduction of the calcium-channel blocker may be appropriate.
Ivacaftor: (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.
Ketamine: (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.
Ketoconazole: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with ketoconazole as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; ketoconazole is a strong/moderate CYP3A4 inhibitor.
Ketoprofen: (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.
Ketorolac: (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.
Labetalol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lanreotide: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin and nifedipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving nifedipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Nifedipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
Lasmiditan: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Lefamulin: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with oral lefamulin as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Lenacapavir: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with lenacapavir as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of nifedipine; monitor for potential reduction in efficacy. Nifedipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of nifedipine; monitor for potential reduction in efficacy. Nifedipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (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. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levobunolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Levoketoconazole: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with ketoconazole as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; ketoconazole is a strong/moderate CYP3A4 inhibitor.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Lidocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Linagliptin; Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Lisdexamfetamine: (Minor) Lisdexamfetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Lithium: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Lonafarnib: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with lonafarnib as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor.
Lopinavir; 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) Lopinavir prolongs the PR interval in some patients; however, the impact on the PR interval when administered 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.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of nifedipine and lumacaftor; ivacaftor and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Lumacaftor; Ivacaftor: (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.
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.
Magnesium: (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.
Mannitol: (Moderate) Nifedipine can have additive hypotensive effects with other antihypertensive agents (including diuretics). This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Maraviroc: (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.
Meclofenamate Sodium: (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.
Mefenamic Acid: (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.
Melatonin: (Moderate) Monitor blood pressure during concomitant calcium-channel blocker and melatonin use. Melatonin may impair the efficacy of calcium-channel blockers. In a placebo-controlled study, melatonin evening ingestion led to significant increases in blood pressure (6.5 mmHg systolic and 4.9 mmHg diastolic) and heart rate (3.9 bpm) throughout the day in patients taking a calcium channel blocker Melatonin appeared to antagonize the antihypertensive effects of the calcium channel blocker.
Meloxicam: (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.
Metformin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Metformin; Repaglinide: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Metformin; Rosiglitazone: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Metformin; Saxagliptin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Metformin; Sitagliptin: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Methohexital: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Methoxsalen: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methylphenidate Derivatives: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of meth ylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Metoprolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Micafungin: (Moderate) Concomitant nifedipine and micafungin administration may increase the systemic exposure and the maximum serum concentration of nifedipine. Nifedipine AUC and Cmax were increased by 18% and 42%, respectively, in the presence of steady-state micafungin compared with nifedipine alone. Patients should be monitored closely for nifedipine-related side effects; nifedipine dosage reduction may be necessary.
Mifepristone: (Moderate) Monitor blood pressure and heart rate if coadministration of nifedipine with mifepristone is necessary. Concurrent use may result in elevated nifedipine concentrations. Nifedipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mitotane: (Major) Avoid coadministration of nifedipine and mitotane and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Nabumetone: (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.
Nadolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Naproxen: (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.
Naproxen; Esomeprazole: (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.
Naproxen; Pseudoephedrine: (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) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Nebivolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Nebivolol; Valsartan: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Nefazodone: (Moderate) Nefazodone is a CYP3A4 inhibitor which theoretically may decrease hepatic clearance and enhance oral bioavailability of nifedipine, a CYP3A4 substrate. In addition, although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring is recommended. Dependent upon clinical response, dosage adjustments of either drug may be necessary.
Nelfinavir: (Moderate) According to the manufacturer of nifedipine, coadministration with nelfinavir 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. If coadministration is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nirmatrelvir; 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.
Nitrates: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (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.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of nifedipine with rifabutin and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. Nifedipine is a CYP3A substrate and rifabutin is a CYP3A inducer.
Oritavancin: (Moderate) Nifedipine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of nifedipine may be reduced if these drugs are administered concurrently.
Oxaprozin: (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.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by calcium-channel blockers. 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 calcium-channel blockers who are susceptible to hypotension.
Pasireotide: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as calcium-channel blockers. Dose adjustments of calcium-channel blockers may be necessary.
Pentobarbital: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
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.
Phenelzine: (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.
Phenobarbital: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Phenytoin: (Major) Avoid coadministration of nifedipine with phenytoin and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Phosphodiesterase inhibitors: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response. For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
Photosensitizing agents (topical): (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Pindolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Pioglitazone: (Minor) Concentrations of nifedipine may be decreased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of nifedipine ER was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with nifedipine ER 30 mg once daily for 4 days resulted in a 13% and 17% reduction in nifedipine ER AUC and Cmax, respectively. In addition, coadministration for 7 days resulted in a 5% and 4% increase in pioglitazone AUC and Cmax, respectively. Patients should be monitored for the desired cardiovascular effects on heart rate, chest pain, or blood pressure; nifedipine dosages may need to be adjusted while the patient is receiving pioglitazone. Close monitoring of blood glucose is also recommended; dosage adjustments in pioglitazone may be needed.
Pioglitazone; Glimepiride: (Minor) Concentrations of nifedipine may be decreased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of nifedipine ER was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with nifedipine ER 30 mg once daily for 4 days resulted in a 13% and 17% reduction in nifedipine ER AUC and Cmax, respectively. In addition, coadministration for 7 days resulted in a 5% and 4% increase in pioglitazone AUC and Cmax, respectively. Patients should be monitored for the desired cardiovascular effects on heart rate, chest pain, or blood pressure; nifedipine dosages may need to be adjusted while the patient is receiving pioglitazone. Close monitoring of blood glucose is also recommended; dosage adjustments in pioglitazone may be needed.
Pioglitazone; Metformin: (Minor) Concentrations of nifedipine may be decreased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of nifedipine ER was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with nifedipine ER 30 mg once daily for 4 days resulted in a 13% and 17% reduction in nifedipine ER AUC and Cmax, respectively. In addition, coadministration for 7 days resulted in a 5% and 4% increase in pioglitazone AUC and Cmax, respectively. Patients should be monitored for the desired cardiovascular effects on heart rate, chest pain, or blood pressure; nifedipine dosages may need to be adjusted while the patient is receiving pioglitazone. Close monitoring of blood glucose is also recommended; dosage adjustments in pioglitazone may be needed. (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin.
Piroxicam: (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.
Posaconazole: (Moderate) Monitor blood pressure and heart rate if coadministration of nifedipine with posaconazole is necessary. Concurrent use may result in elevated nifedipine concentrations. Nifedipine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
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. The use of alpha-blockers with verapamil can lead to excessive hypotension; In addition, verapamil has been reported to increase the AUC and Cmax of prazosin.
Prilocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Primidone: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
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.
Promethazine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Propafenone: (Major) Because both propafenone and nifedipine have negative inotropic properties, additive effects are possible especially in patients with abnormal ventricular function. It may be prudent to monitor patients closely if nifedipine is used with other drugs that are negative inotropes such as propafenone.
Propofol: (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.
Propranolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Quinidine: (Moderate) Nifedipine has been reported to rarely decrease quinidine serum concentrations. Quinidine concentrations may decrease by 20% to 40% when nifedipine is added, and potentially increase after nifedipine is withdrawn. 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.
Ranitidine: (Moderate) Cimetidine can increase nifedipine exposure by inhibiting hepatic metabolism of nifedipine. Ranitidine has been shown to have a similar, but lesser, effect on nifedipine pharmacokinetics. Clinicians should be alert for exaggerated nifedipine effects if ranitidine is coadministered.
Rasagiline: (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 during concurrent use of an MAOI and a calcium-channel blocker.
Remifentanil: (Moderate) The risk of significant hypotension and/or bradycardia during therapy with remifentanil may be increased in patients receiving calcium-channel blockers due to additive hypotensive effects.
Ribociclib: (Moderate) Monitor blood pressure if coadministration of nifedipine with ribociclib is necessary; consider decreasing the dose of nifedipine if appropriate. Nifedipine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Concomitant use may increase nifedipine exposure.
Ribociclib; Letrozole: (Moderate) Monitor blood pressure if coadministration of nifedipine with ribociclib is necessary; consider decreasing the dose of nifedipine if appropriate. Nifedipine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Concomitant use may increase nifedipine exposure.
Rifabutin: (Major) Avoid coadministration of nifedipine with rifabutin and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. Nifedipine is a CYP3A substrate and rifabutin is a CYP3A inducer.
Rifampin: (Major) Avoid coadministration of nifedipine with rifampin, and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and rifampin is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Rifapentine: (Major) Avoid coadministration of nifedipine with rifapentine and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Risperidone: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ritlecitinib: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with ritlecitinib as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor.
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.
Saquinavir: (Moderate) According to the manufacturer of nifedipine, coadministration with saquinavir 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. If coadministration is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Secobarbital: (Major) Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and barbiturates are strong CYP3A4 inducers. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Sevoflurane: (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.
Sildenafil: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response. For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
Silodosin: (Moderate) Monitor for adverse effects if silodosin is coadministered with nifedipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by calcium-channel blockers. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of results.
Sotalol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of nifedipine and St. John's Wort, Hypericum perforatum, and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Sufentanil: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with nifedipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving nifedipine.
Sulindac: (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.
Sumatriptan; Naproxen: (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.
Tacrolimus: (Moderate) Tacrolimus is metabolized by CYP3A4 isoenzyme. CYP3A4 is the major isoenzyme that metabolizes nifedipine. When coadministered with nifedipine, tacrolimus whole blood trough concentrations are increased. In a retrospective study of liver transplant patients with hypertension, nifedipine decreased the daily and cumulative dosage requirements of tacrolimus by 26%, 29%, and 38% at 3, 6, and 12 months, respectively, compared with the dosage for patients who did not receive nifedipine. It is recommended that tacrolimus blood concentrations be closely monitored when nifedipine and tacrolimus are administered concomitantly.
Tadalafil: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response. For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
Tamsulosin: (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. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Temsirolimus: (Moderate) Monitor for signs and symptoms of angioedema if temsirolimus is administered concomitantly with nifedipine; an increase in temsirolimus-related adverse reactions may also occur. Angioedema has been reported in patients taking mammalian target of rapamycin (mTOR) inhibitors in combination with another calcium channel blocker.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
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.
Tezacaftor; Ivacaftor: (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.
Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Timolol: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Tipranavir: (Moderate) Tipranavir may interact with certain calcium-channel blockers. Tipranavir may interact with calcium-channel blockers that undergo significant metabolism via CYP3A4, including nifedipine. Cautious dose titration of these calcium-channel blockers should be considered; the patient should be monitored for the proper clinical responses to calcium-channel blocker therapy.
Tolmetin: (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.
Trandolapril; Verapamil: (Moderate) Diltiazem has been reported to increase the plasma level and hypotensive effects of nifedipine via CYP3A4 inhibition. Verapamil may also inhibit CYP3A4 metabolism of nifedipine.
Tranylcypromine: (Major) Avoid concomitant use of calcium-channel blockers and tranylcypromine due to the risk of additive hypotension. Potential for this interaction persists for up to 10 days after discontinuation of tranylcypromine (or 4 to 5 half-lives after discontinuation of the calcium-channel blocker). If a medication-free interval is not feasible, initiate therapy at the lowest appropriate dose and monitor blood pressure closely.
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.
Tucatinib: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with tucatinib as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor.
Urea: (Moderate) Nifedipine can have additive hypotensive effects with other antihypertensive agents (including diuretics). This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Valdecoxib: (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.
Vardenafil: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response. For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
Verapamil: (Moderate) Diltiazem has been reported to increase the plasma level and hypotensive effects of nifedipine via CYP3A4 inhibition. Verapamil may also inhibit CYP3A4 metabolism of nifedipine.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with calcium channel blockers is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use with calcium channel blockers could enhance the rate of verteporfin uptake by the vascular endothelium, resulting in enhanced photosensitivity.
Vincristine Liposomal: (Major) Use caution if coadminsitration of nifedipine is necessary with vincristine and monitor for vincristine toxicity. In a pharmacokinetic study of 26 patients with solid tumors and normal renal and hepatic function, vincristine 2 mg IV was administered alone (n = 14) or with nifedipine 10 mg by mouth three times daily for 3 days before and 7 days after (n = 12). Coadministration of nifedipine significantly increased vincristine AUC (10 +/- 2.91 mcg x min/ml vs 2.9 +/- 0.86 mcg x min/ml; p = < 0.001) and terminal half-life (85.56 +/- 23.51 hours vs 21.72 +/- 9.61 hours; p < 0.05) compared with vincristine alone; additionally, the plasma clearance was significantly reduced in patients treated with nifedipine (309.54 +/- 95.46 vs 985.06 +/- 258.6 ml/min/m2; p < 0.01). The mechanism of this interaction is poorly understood.
Vincristine: (Major) Use caution if coadminsitration of nifedipine is necessary with vincristine and monitor for vincristine toxicity. In a pharmacokinetic study of 26 patients with solid tumors and normal renal and hepatic function, vincristine 2 mg IV was administered alone (n = 14) or with nifedipine 10 mg by mouth three times daily for 3 days before and 7 days after (n = 12). Coadministration of nifedipine significantly increased vincristine AUC (10 +/- 2.91 mcg x min/ml vs 2.9 +/- 0.86 mcg x min/ml; p = < 0.001) and terminal half-life (85.56 +/- 23.51 hours vs 21.72 +/- 9.61 hours; p < 0.05) compared with vincristine alone; additionally, the plasma clearance was significantly reduced in patients treated with nifedipine (309.54 +/- 95.46 vs 985.06 +/- 258.6 ml/min/m2; p < 0.01). The mechanism of this interaction is poorly understood.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin and nifedipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving nifedipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Nifedipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
Voriconazole: (Moderate) Monitor blood pressure and heart rate if coadministration of nifedipine with voriconazole is necessary. Concurrent use may result in elevated nifedipine concentrations. Nifedipine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Voxelotor: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with voxelotor as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Minor) Concurrent administration of highly protein-bound agents such as nifedipine can theoretically displace warfarin from its binding sites, with potential for increased anticoagulation effects. The manufacturer of nifedipine reports rare cases of increased prothrombin time when nifedipine was administered to patients taking warfarin; the relationship to nifedipine is uncertain.
Zafirlukast: (Minor) Zafirlukast is a CYP3A4 inhibitor which theoretically may decrease hepatic clearance and enhance oral bioavailability of nifedipine, a CYP3A4 substrate.
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.
ardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
Verapamil: (Moderate) Diltiazem has been reported to increase the plasma level and hypotensive effects of nifedipine via CYP3A4 inhibition. Verapamil may also inhibit CYP3A4 metabolism of nifedipine.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with calcium channel blockers is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use with calcium channel blockers could enhance the rate of verteporfin uptake by the vascular endothelium, resulting in enhanced photosensitivity.
Vincristine Liposomal: (Major) Use caution if coadminsitration of nifedipine is necessary with vincristine and monitor for vincristine toxicity. In a pharmacokinetic study of 26 patients with solid tumors and normal renal and hepatic function, vincristine 2 mg IV was administered alone (n = 14) or with nifedipine 10 mg by mouth three times daily for 3 days before and 7 days after (n = 12). Coadministration of nifedipine significantly increased vincristine AUC (10 +/- 2.91 mcg x min/ml vs 2.9 +/- 0.86 mcg x min/ml; p = < 0.001) and terminal half-life (85.56 +/- 23.51 hours vs 21.72 +/- 9.61 hours; p < 0.05) compared with vincristine alone; additionally, the plasma clearance was significantly reduced in patients treated with nifedipine (309.54 +/- 95.46 vs 985.06 +/- 258.6 ml/min/m2; p < 0.01). The mechanism of this interaction is poorly understood.
Vincristine: (Major) Use caution if coadminsitration of nifedipine is necessary with vincristine and monitor for vincristine toxicity. In a pharmacokinetic study of 26 patients with solid tumors and normal renal and hepatic function, vincristine 2 mg IV was administered alone (n = 14) or with nifedipine 10 mg by mouth three times daily for 3 days before and 7 days after (n = 12). Coadministration of nifedipine significantly increased vincristine AUC (10 +/- 2.91 mcg x min/ml vs 2.9 +/- 0.86 mcg x min/ml; p = < 0.001) and terminal half-life (85.56 +/- 23.51 hours vs 21.72 +/- 9.61 hours; p < 0.05) compared with vincristine alone; additionally, the plasma clearance was significantly reduced in patients treated with nifedipine (309.54 +/- 95.46 vs 985.06 +/- 258.6 ml/min/m2; p < 0.01). The mechanism of this interaction is poorly understood.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin and nifedipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving nifedipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Nifedipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
Voriconazole: (Moderate) Monitor blood pressure and heart rate if coadministration of nifedipine with voriconazole is necessary. Concurrent use may result in elevated nifedipine concentrations. Nifedipine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Voxelotor: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with voxelotor as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Minor) Concurrent administration of highly protein-bound agents such as nifedipine can theoretically displace warfarin from its binding sites, with potential for increased anticoagulation effects. The manufacturer of nifedipine reports rare cases of increased prothrombin time when nifedipine was administered to patients taking warfarin; the relationship to nifedipine is uncertain.
Zafirlukast: (Minor) Zafirlukast is a CYP3A4 inhibitor which theoretically may decrease hepatic clearance and enhance oral bioavailability of nifedipine, a CYP3A4 substrate.
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.
How Supplied
Adalat CC/Afeditab CR/Nifediac CC/Nifedical XL/Nifedipine/Procardia XL Oral Tab ER: 30mg, 60mg, 90mg
Adalat/Nifedipine/Procardia Oral Cap: 10mg, 20mg
Maximum Dosage
90 mg/day PO for Procardia XL or 180 mg/day PO for immediate-release capsules for angina; 90 mg/day PO for most extended-release tabs and 120 mg/day PO for Procardia XL for hypertension.
Elderly90 mg/day PO for Procardia XL or 180 mg/day PO for immediate-release capsules for angina; 90 mg/day PO for most extended-release tabs and 120 mg/day PO for Procardia XL for hypertension.
AdolescentsSafety and efficacy have not been established; however, up to 3 mg/kg/day PO (not to exceed 180 mg/day) for extended-release tablets has been used off-label for hypertension; 0.5 mg/kg/dose (not to exceed 10 mg/dose) has been used off-label for hypertensive urgency/emergency.
ChildrenSafety and efficacy have not been established; however, up to 3 mg/kg/day PO (not to exceed 180 mg/day) for extended-release tablets has been used off-label for hypertension; 0.5 mg/kg/dose (not to exceed 10 mg/dose) has been used off-label for hypertensive urgency/emergency.
Mechanism Of Action
Mechanism of Action: Like other calcium-channel antagonists, nifedipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores, which are selective for specific ions. Serum calcium levels remain unchanged. It is believed that nifedipine inhibits this influx by physically plugging the channel. While verapamil and diltiazem exert balanced effects on calcium channels in the SA node, AV node, and vasculature, nifedipine and other members of the dihydropyridine group act predominantly on the vasculature, making these agents more potent peripheral vasodilators. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries. This results in increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.Although these drugs originally were believed to improve oxygen supply, it now appears that their effectiveness as anti-ischemic agents arises from their ability to alter the systemic balance between supply and demand. Reduced afterload and reduced myocardial wall tension lead to reduced myocardial oxygen demand, which now seems to best explain the benefit of nifedipine and other dihydropyridines in the treatment of angina. Thus, nifedipine increases myocardial oxygen supply (secondary to coronary vasodilation) and decreases myocardial oxygen demand (secondary to decreased afterload). Nifedipine appears particularly effective in treating variant angina (i.e., vasospastic angina) due to this ability to increase myocardial oxygen supply by inducing coronary vasodilation. The effectiveness of nifedipine in treating chronic stable angina, on the other hand, is related to the decrease in myocardial oxygen demand secondary to decreased afterload.Nifedipine has no clinical effect on AV conduction, which may be due to its inhibition of phosphodiesterase. This intracellular mechanism of nifedipine actually enhances calcium inflow and counteracts its own inhibitory effects on calcium influx at the membrane surface. Also, phosphodiesterase inhibition causes additional relaxation of vascular smooth muscle. Thus, nifedipine is more potent than verapamil as a peripheral vasodilator but has negligible effects on AV nodal conduction. Negative inotropic effects rarely are noted clinically, presumably due to a reflex increase in heart rate in response to nifedipine's vasodilatory activity. Nifedipine therapy usually does not affect cardiovascular parameters in patients with normal ventricular function, but patients with decreased left ventricular function can experience an increase in ejection fraction and a decrease in left ventricular filling pressures. In general, calcium-channel blockers exert favorable effects on LVH, and do not worsen insulin resistance or exert detrimental effects on the lipid profile.
Pharmacokinetics
Nifedipine is administered orally and sublingually. It is relatively well distributed, including into breast milk. Nifedipine is protein-bound in a concentration-dependent way, ranging from 92% to 98%. Hepatic metabolism is rapid and complete, causing the formation of 2 inactive metabolites that, along with the parent drug, are excreted primarily in the urine and, to a lesser extent, the feces. Less than 5% is eliminated as unchanged drug. The elimination half-life of nifedipine is approximately 2 to 5 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Nifedipine is a CYP3A4 substrate, and its metabolism may be affected by CYP3A4 inhibitors or inducers.
Nifedipine is rapidly and well absorbed (90%) following an oral dose but undergoes extensive first-pass metabolism, resulting in a bioavailability of 50% to 70%. The bioavailability of the sustained-release tablet ("gastrointestinal therapeutic system [GITS]") relative to the capsule is 86% after chronic administration. The bioavailability of nifedipine does not appear to be affected by food. Co-administration of nifedipine with grapefruit juice increases the AUC and peak plasma concentrations of nifedipine by 2-fold, with no change in half-life. Bioavailability is substantially increased (up to a 100% increase) in the presence of hepatic impairment. Decreases in gastrointestinal transit time can significantly alter the absorption characteristics of the sustained-release formulation in a relatively unpredictable fashion by increasing the time available for the osmotically driven release to occur.
Sublingual administration of nifedipine liquid (expressed from regular-release capsules) to achieve rapid decreases in blood pressure, such as in the case of hypertensive urgency, has generated much controversy and confusion and is not recommended. There is little difference in the bioavailability when nifedipine capsules are swallowed whole or if they are bitten and swallowed, or bitten and held sublingually. Biting through the capsule does, however, result in slightly earlier plasma concentrations (within 10 minutes) than if capsules were swallowed intact.
Onset of hypotensive effects occurs in 30 minutes to 1 hour after administration of regular-release capsules, with peak effects occurring within 30 minutes to 2 hours. With the sustained-release tablet, serum concentrations do not peak for 6 hours, and hypotensive effects are correspondingly delayed. Duration of pharmacodynamic activity for the immediate-release preparation is approximately 8 hours. The extended-release tablet is designed to release nifedipine continuously in a zero-order process. Once-daily dosing is possible with this dosage form.
Pregnancy And Lactation
There are no adequate and well-controlled studies of nifedipine use in pregnant women. In animal studies involving rats and rabbits, nifedipine has been shown to be teratogenic. Nifedipine was associated with various embryotoxic, placentotoxic, and fetotoxic effects, including stunted fetuses, embryonic deaths, and fetal deaths in rats, mice and rabbits; rib deformities and cleft palates in mice; small placentas and underdeveloped chorionic villi in monkeys; and prolonged pregnancy/decreased neonatal survival in rats. Nifedipine should only be used during pregnancy if the potential benefit justifies the potential risk.
Because nifedipine is excreted in human milk, the manufacturer does not recommend breast-feeding during nifedipine therapy. Based off of data from a single mother-infant pair, it has been estimated that the amount of drug that would appear in the breast-milk is less than 5% of the maternal therapeutic dose. However, neonatal myocardium is very sensitive to changes in calcium status, and the therapeutic dose for a neonate is unknown. The authors further concluded that delaying breast-feeding or expressing milk for 3 to 4 hours after a dose would significantly reduce the amount of drug ingested by a nursing infant. Previous recommendations from The American Academy of Pediatrics (AAP) listed nifedipine as usually compatible with breast-feeding. Nifedipine has been used to treat Raynaud's phenomenon of the nipple to decrease the pain associated with breast-feeding. 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 ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.