Nifedipine

What it is

Nifedipine is a synthetic dihydropyridine that blocks the slow calcium channels in heart muscle and the muscle wall of arteries, so less calcium gets into those cells and they relax. It does this without changing the amount of calcium in the blood. It comes in two very different forms that behave almost like different drugs: short-acting capsules that release the drug all at once, and extended-release tablets built as an osmotic pump that delivers the drug at a near-constant rate over 24 hours. The distinction matters, because the harm evidence attaches mainly to the short-acting form. It is broken down by CYP3A4, which is why grapefruit juice roughly doubles blood levels.

What the research says

Nifedipine lowers blood pressure and relieves angina caused by coronary artery spasm. The largest outcome trial, INSIGHT, randomised 6,321 high-risk hypertensive patients and found once-daily long-acting nifedipine as good as a diuretic combination for preventing cardiovascular events (6.3% versus 5.8%; relative risk 1.10, 95% CI 0.91 to 1.34), with more withdrawals for ankle swelling. In stable angina the 7,665-patient ACTION trial found no effect on its primary endpoint of death, myocardial infarction and other major events. The most important negative finding concerns the old short-acting capsules: a meta-analysis of 16 secondary-prevention trials found mortality rose with dose, reaching a risk ratio of 2.83 at 80 mg a day. Off-label it is used to delay preterm birth, where Cochrane found fewer births within 48 hours but no difference in perinatal deaths and criticised the lack of blinding; for Raynaud attacks, where the average benefit is 2.8 to 5 fewer attacks a week; and to prevent high-altitude pulmonary oedema, where a small randomised trial found oedema in 7 of 11 on placebo versus 1 of 10 on nifedipine. Ankle swelling is the commonest problem, in roughly 10% to 30% of people depending on dose.

Evidence grade: Well established.

How it works

Drug class: Dihydropyridine calcium channel blocker (calcium ion influx inhibitor)

Heart muscle and the muscle in artery walls need calcium to flow into their cells before they can contract. Nifedipine blocks the specific channels that let that calcium in, so the arteries relax and widen, blood pressure falls, and the heart has less resistance to pump against. It does this without altering the calcium level in your blood, so it has nothing to do with dietary calcium. It also widens the coronary arteries and is a strong blocker of coronary spasm, which is why it works for vasospastic angina. The label is candid that spasm relief is probably not the main mechanism in ordinary effort-related angina. (Source 1)

What it is used for

• In the 6,321-patient INSIGHT trial, long-acting nifedipine and a diuretic combination were equally effective at preventing cardiovascular and cerebrovascular events, with mean blood pressure falling from 173/99 to 138/82 mmHg. The trialists concluded the choice between them can rest on tolerability rather than safety or efficacy. Evidence: established. (Source 2)
• Nifedipine is a potent blocker of coronary artery spasm, which is the rationale for this use. We found no modern placebo-controlled outcome trial in confirmed vasospastic angina during this search; the evidence base here is older and smaller than for hypertension. Evidence: limited. (Source 1)
• Adding long-acting nifedipine to standard treatment did not change the rate of death, heart attack or other major events in the 7,665-patient ACTION trial. It did reduce the need for coronary angiography and interventions, and had no effect on myocardial infarction rate. Evidence: disputed. (Source 3)
• Cochrane's 38-trial review, mostly of nifedipine, found fewer births within 48 hours than with placebo and fewer maternal side effects than with betamimetics, but no difference in perinatal mortality and limited long-term infant data. Only one of the 38 trials blinded the intervention, which the reviewers say weakens the whole body of evidence. Evidence: limited. (Source 4)
• A meta-analysis of 18 small randomised trials found calcium channel blockers reduced attacks and their severity, but the authors describe the effect as small, on average 2.8 to 5 fewer attacks a week and about a third less severe, with possible bias from unstudied order effects in crossover designs. Evidence: limited. (Source 5)
• In a randomised double-blind trial of 21 mountaineers with a history of the condition, slow-release nifedipine prevented recurrence in 9 of 10 while 7 of 11 on placebo developed oedema. Small, but a clean randomised result with a large effect. Evidence: limited. (Source 6)

Interactions

• Grapefruit and grapefruit juice (pharmacokinetic study): Grapefruit juice raises nifedipine blood levels substantially, which can exaggerate the blood-pressure-lowering effect. A 16-volunteer crossover study found the juice increased bioavailability and also slowed stomach emptying, producing a second concentration peak. The manufacturer advises avoiding grapefruit and grapefruit juice altogether while taking nifedipine. (Source 7)
• Grapefruit juice (the manufacturer's position) (label): The labelling quantifies it: roughly a doubling of nifedipine exposure and peak level, with no change in half-life, attributed to inhibition of CYP3A4 in the gut wall and liver on first pass. (Source 8)
• CYP3A4 inducers, phenytoin being the studied example (St John's wort works by the same mechanism) (pharmacokinetic study): Enzyme inducers strip nifedipine out of the blood and can leave blood pressure uncontrolled. Phenytoin cut nifedipine exposure by about 70%, and the label extends the warning to any known CYP3A4 inducer. St John's wort is a herbal CYP3A4 inducer, but we found no published human study of it with nifedipine, so treat that combination as theoretical rather than measured. (Source 9)
• Cimetidine (an over-the-counter acid blocker in some countries) (pharmacokinetic study): Cimetidine inhibits the liver enzyme that clears nifedipine, raising peak levels by about 80%. Ranitidine had a smaller, non-significant effect. (Source 10)
• Beta blockers and other blood-pressure-lowering medicines (label): Combining them can lower blood pressure too far. The labelling asks for close blood pressure monitoring when the drugs are used together, and notes that excessive, poorly tolerated hypotension has happened, usually during dose titration. (Source 11)
• Calcium supplements (theoretical): Often assumed to be a problem, but nifedipine does not act on the calcium in your blood at all. The labelling states the drug blocks calcium entry into muscle cells without altering serum calcium concentrations. We found no human trial showing that a calcium supplement blunts nifedipine's effect, so this should be read as an absence of evidence rather than proof of no interaction. (Source 1)

Stopping it

• The literature we read describes no dependence or withdrawal syndrome for nifedipine itself. The withdrawal warning on the label runs the other way: beta blockers should be tapered rather than stopped abruptly before nifedipine is started, because beta blocker withdrawal can cause a flare of angina that nifedipine will not prevent and has sometimes seemed to worsen. (Source 12)
• Because the dose is reached by titration against blood pressure over a week or two, changes in either direction are made gradually and with blood pressure measurement rather than stopped at once. (Source 13)

What goes wrong

In that same trial, significantly more people stopped nifedipine than the comparator because of ankle and leg swelling. (Source 2)

• Randomized trial, High certainty.
• Size: 6,321 patients.
• Who: High-risk hypertensive patients aged 55 to 80.
• How long: Trial duration to primary endpoint.
• Result: 8% excess of withdrawals from the nifedipine group because of peripheral oedema, 725 versus 518, p<0.0001; serious adverse events were conversely more frequent on co-amilozide, 880 versus 796, p=0.02.
• Funding: not stated in the recorded passage.

There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02).

Short-acting nifedipine at moderate to high doses increased total mortality in people with coronary heart disease, and the risk rose with the dose. (Source 14)

• Meta-analysis, Moderate certainty.
• Size: 16 randomised secondary-prevention trials of nifedipine with mortality data.
• Who: Patients with coronary heart disease.
• How long: Varied by trial.
• Result: Overall risk ratio for total mortality 1.16 (95% CI 1.01 to 1.33); by daily dose 1.06 (0.89 to 1.27) at 30 to 50 mg, 1.18 (0.93 to 1.50) at 60 mg and 2.83 (1.35 to 5.93) at 80 mg; formal dose-response test P = .01.
• Funding: not stated.

For daily doses of 30 to 50, 60, and 80 mg, the risk ratios for total mortality were 1.06 (95% CI, 0.89 to 1.27), 1.18 (95% CI, 0.93 to 1.50), and 2.83 (95% CI, 1.35 to 5.93), respectively.

The authors of that meta-analysis stated plainly that short-acting nifedipine in moderate to high doses causes increased total mortality in coronary disease, and that long-term safety data were lacking for most calcium antagonists. (Source 15)

• Meta-analysis, Moderate certainty.
• Size: 16 randomised trials.
• Who: Patients with coronary disease.
• How long: Varied.
• Result: Proposed mechanisms included proischaemic effect, negative inotropy, marked hypotension, prohaemorrhagic and possibly proarrhythmic effects.
• Funding: not stated.

In patients with coronary disease, the use of short-acting nifedipine in moderate to high doses causes an increase in total mortality.

Ankle and leg swelling is the characteristic dose-dependent adverse effect, affecting roughly 10% to 30% of users depending on dose. (Source 16)

• Official position, Certainty not rated.
• Size: Not stated in the label passage; incidence range given across doses to 180 mg.
• Who: Patients taking extended-release nifedipine.
• How long: Not stated.
• Result: Mild to moderate peripheral oedema in approximately 10% to about 30% at the highest dose studied (180 mg), described as a local vasodilator effect rather than heart failure.
• Funding: regulator-approved labelling.

Mild to moderate peripheral edema occurs in a dose dependent manner with an incidence ranging from approximately 10% to about 30% at the highest dose studied (180 mg).

In placebo-controlled studies of the short-acting capsules, dizziness, flushing and swelling were all clearly more common on drug than on placebo. (Source 17)

• Official position, Certainty not rated.
• Size: 226 patients on nifedipine capsules versus 235 on placebo in the label's pooled table.
• Who: Patients in multiple-dose US and foreign controlled studies of nifedipine capsules.
• How long: Not stated.
• Result: In the label's table: dizziness or lightheadedness 27% versus 15%, flushing or heat sensation 25% versus 8%, headache 23% versus 20%, muscle cramps or tremor 8% versus 3%, peripheral oedema 7% versus 1%.
• Funding: regulator-approved labelling.

adverse effects were frequent but generally not serious and rarely required discontinuation of therapy or dosage adjustment. Most were expected consequences of the vasodilator effects of nifedipine.

The osmotic-pump tablet shell can obstruct the gut, occasionally needing surgery, even in people with no previous bowel disease. (Source 18)

• Case series, Very low certainty.
• Size: Spontaneous postmarketing reports; no denominator given.
• Who: Patients taking PROCARDIA XL extended-release tablets.
• How long: Not stated.
• Result: No rate given; obstruction requiring hospitalisation and surgery including bezoar removal, and tablet adherence to the gut wall with ulceration.
• Funding: regulator-approved labelling.

Gastrointestinal obstruction resulting in hospitalization and surgery, including the need for bezoar removal, has occurred in association with PROCARDIA XL, even in patients with no prior history of gastrointestinal disease

What the evidence supports

The same trial did find fewer coronary procedures on nifedipine, which is why it is not a wholly null result. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 7,665 patients.
• Who: Patients with treated stable symptomatic coronary disease.
• How long: Mean 4.9 years.
• Result: Death and any cardiovascular event or procedure 9.32 versus 10.50 per 100 patient-years (hazard ratio 0.89, 95% CI 0.83 to 0.95, p=0.0012), mainly from fewer coronary angiographies and interventions, despite an increase in peripheral revascularisation.
• Funding: not stated in the recorded passage.

The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine, despite an increase in peripheral revascularisation.

For delaying preterm birth, calcium channel blockers beat placebo or no treatment for postponing birth by 48 hours, at the cost of far more maternal side effects. (Source 4)

• Systematic review, Low certainty.
• Size: 38 trials with 3,550 women overall; the placebo comparison rests on two small trials, the maternal adverse effect estimate on one trial of 89 women.
• Who: Women in labour between 20 and 36 completed weeks' gestation; 35 of the 38 trials used nifedipine.
• How long: To birth and neonatal outcomes; one trial followed children to 9 to 12 years.
• Result: Birth less than 48 hours after trial entry RR 0.30 (95% CI 0.21 to 0.43); maternal adverse effects RR 49.89 (95% CI 3.13 to 795.02); preterm birth under 37 weeks not pooled because of heterogeneity, one placebo trial showing no difference (RR 0.96, 0.89 to 1.03)
• Funding: not stated.

Two small trials comparing CCBs with placebo or no treatment showed a significant reduction in birth less than 48 hours after trial entry (RR 0.30, 95% CI 0.21 to 0.43) and an increase in maternal adverse effects (RR 49.89, 95% CI 3.13 to 795.02, one trial of 89 women).

For primary Raynaud's phenomenon, nifedipine and related drugs reduce attacks, but the meta-analysts describe the benefit as small. (Source 5)

• Meta-analysis, Low certainty.
• Size: 18 of 31 randomised trials eligible (13 nifedipine versus placebo, 5 other calcium channel blockers versus placebo); the pooled frequency analysis used 17 trials and the severity analysis 8 trials; 361 participants in the non-nifedipine comparison.
• Who: Patients with primary Raynaud's phenomenon.
• How long: Trials of more than 2 days with fewer than 35% dropouts.
• Result: Weighted mean difference in attacks per week for all calcium channel blockers -5.00 (95% CI -9.02 to -0.99), or -2.80 (-3.90 to -1.70) allowing for heterogeneity, and -6.05 (-11.19 to -0.19) for nifedipine alone; severity on a 10 cm visual analogue scale -1.39 (-2.20 to -0.58) overall and -1.81 (-3.08 to -0.54) for nifedipine.
• Funding: not stated.

Limit of this finding: The review reports two different figures for the same thing: 5.0 fewer attacks a week (-5.00, -9.02 to -0.99), then 2.8 fewer (-2.80, -3.90 to -1.70) once the differences between trials are allowed for, and its conclusion simply gives the range 2.8 to 5.0. The nifedipine-only figure, -6.05 (-11.19 to -0.19), is not centred inside its own interval, which is an arithmetic oddity in the paper. Treat the benefit as a rough range of roughly three to five fewer attacks a week, not as a single number. The "n =" values quoted here are numbers of trials, not numbers of people.

The efficacy of CCBs for reducing severity and frequency of ischaemic attacks in primary RP is small (average of 2.8 to 5.0 fewer attacks per week and a 33% reduction in severity).

Prophylactic slow-release nifedipine prevented recurrence of high-altitude pulmonary oedema in susceptible mountaineers. (Source 6)

• Randomized trial, Low certainty.
• Size: 21 mountaineers (10 nifedipine, 11 placebo)
• Who: Mountaineers with a history of radiographically documented high-altitude pulmonary oedema, 1 woman and 20 men.
• How long: Rapid ascent within 22 hours to 4,559 m, then three days at altitude.
• Result: Pulmonary oedema in 7 of 11 on placebo versus 1 of 10 on nifedipine (P = 0.01); systolic pulmonary artery pressure 41 +/- 8 versus 53 +/- 16 mmHg (P = 0.01); alveolar-arterial gradient 6.6 +/- 3.8 versus 11.8 +/- 4.4 mmHg (P less than 0.001)
• Funding: not stated.

Limit of this finding: This was a 21-person trial in mountaineers who had already had radiographically confirmed high-altitude pulmonary oedema before, climbing to 4,559 m within 22 hours. That is a highly selected group on an unusually fast ascent, so the result says nothing about ordinary trekkers or about people who have never had the condition.

Seven of the 11 subjects who received placebo but only 1 of the 10 subjects who received nifedipine had pulmonary edema at 4559 m (P = 0.01).

What the evidence does not support

Adding long-acting nifedipine to standard treatment of stable angina did not improve major cardiovascular event-free survival. (Source 3)

• Randomized trial, High certainty.
• Size: 7,665 patients (3,825 nifedipine GITS 60 mg once daily, 3,840 placebo)
• Who: Patients with treated stable symptomatic coronary disease.
• How long: Mean follow-up 4.9 years (SD 1.1)
• Result: Deaths 310 versus 291 (1.64 versus 1.53 per 100 patient-years; hazard ratio 1.07, 95% CI 0.91 to 1.25, p=0.41); primary endpoint 4.60 versus 4.75 per 100 patient-years (0.97, 0.88 to 1.07, p=0.54); no effect on myocardial infarction rate.
• Funding: not stated in the recorded passage; ACTION was an industry-sponsored trial of nifedipine GITS.

Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival.

That same review found no reduction in perinatal deaths, and warned that the lack of blinding weakens the entire body of tocolysis evidence. (Source 19)

• Systematic review, Low certainty.
• Size: 38 trials, 3,550 women; blinding of intervention and outcome assessment in only one trial.
• Who: Women in preterm labour.
• How long: To birth, neonatal period, and in one trial to age 9 to 12.
• Result: No difference shown in perinatal mortality; comparisons against other tocolytics showed no significant reduction in birth within 48 hours or perinatal mortality; longer-term outcome data limited.
• Funding: not stated.

However, it must be noted that no difference was shown in perinatal mortality, and data on longer-term outcomes were limited. Further, the lack of blinding of the intervention diminishes the strength of this body of evidence.

Where the evidence is mixed

Long-acting nifedipine prevented cardiovascular events about as well as a diuretic combination in high-risk hypertension, with no difference reaching significance. (Source 2)

• Randomized trial, High certainty.
• Size: 6,321 patients (3,157 nifedipine GITS, 3,164 co-amilozide)
• Who: Patients aged 55 to 80 with hypertension and at least one additional cardiovascular risk factor, in Europe and Israel.
• How long: Prospective double-blind trial to a primary composite endpoint.
• Result: Primary outcome 200 (6.3%) versus 182 (5.8%); 18.2 versus 16.5 events per 1,000 patient-years; relative risk 1.10 (95% CI 0.91 to 1.34), p=0.35; mean blood pressure fell from 173/99 to 138/82 mmHg; deaths 176 versus 172 (p=0.81)
• Funding: not stated in the recorded passage; INSIGHT was an industry-sponsored trial of nifedipine GITS.

Primary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35).

The same review flagged its own weaknesses: mostly small crossover trials in which order effects were not examined, and possibly under-dosed. (Source 5)

• Meta-analysis, Low certainty.
• Size: 18 trials pooled; 361 participants in the comparison of other calcium channel blockers versus placebo.
• Who: Primary Raynaud's phenomenon.
• How long: Varied.
• Result: Authors note possible bias from unexamined order effects and a possibly small effect size due to low dosing.
• Funding: not stated.

Limit of this finding: The "n =" figures in this paper count trials, not participants, which is easy to misread: the frequency analysis pooled 17 trials and the severity analysis 8 trials. The authors also flag that most trials were crossovers in which order effects were never examined, and that doses may have been too low, so the size of the benefit is uncertain in both directions.

Most trials were crossover trials in which order effect was not studied; this may have introduced bias.

Where the research disagrees

Whether nifedipine is safe in coronary heart disease

• Furberg, Psaty and Meyer, Circulation 1995, dose-response meta-analysis of 16 randomised secondary-prevention trials of short-acting nifedipine: In patients with coronary disease, the use of short-acting nifedipine in moderate to high doses causes an increase in total mortality. (Source 15)
• Poole-Wilson and colleagues, ACTION, Lancet 2004, 7,665-patient double-blind placebo-controlled trial of the long-acting formulation over a mean 4.9 years: Nifedipine GITS is safe and reduces the need for coronary angiography and interventions. (Source 3)

Whether nifedipine should be used to delay preterm birth

• Flenady and colleagues, Cochrane 2014, on the benefit, systematic review of 38 randomised trials: Calcium channel blockers (mainly nifedipine) for women in preterm labour have benefits over placebo or no treatment in terms of postponement of birth thus, theoretically, allowing time for administration of antenatal corticosteroids and transfer to higher level care. (Source 19)
• The same reviewers, on the limits, the same 38 trials, only one of which blinded the intervention: However, it must be noted that no difference was shown in perinatal mortality, and data on longer-term outcomes were limited. Further, the lack of blinding of the intervention diminishes the strength of this body of evidence. (Source 19)

How much

• Reference intake: Dose is set by the prescriber, not by the reader. As a position, the FDA-approved PROCARDIA XL labelling (Pfizer) says therapy for either hypertension or angina is started at 30 or 60 mg once daily and titrated over 7 to 14 days. (Source 13)
• Upper limit: There is no upper intake level in the nutritional sense. As a position, the PROCARDIA XL labelling states that titration above 120 mg a day is not recommended, and that experience above 90 mg in angina patients is limited. (Source 13)
• Studied: INSIGHT randomised patients to nifedipine 30 mg in a long-acting gastrointestinal-transport-system formulation, with dose doubling as needed. (Source 2)
• Studied: ACTION used nifedipine GITS 60 mg once daily added to conventional angina treatment for a mean of 4.9 years. (Source 3)
• Studied: The high-altitude pulmonary oedema trial used 20 mg of a slow-release preparation every 8 hours during and after a rapid ascent to 4,559 m. (Source 6)
• Studied: The mortality meta-analysis examined short-acting nifedipine at daily doses of 30 to 50, 60 and 80 mg. (Source 14)

A common belief, and what the research shows

The belief: Nifedipine is a calcium blocker, so it lowers the calcium in my blood and I should stop my calcium supplement. And since it treats angina, it must protect the heart.

What the research shows: Both parts are wrong. On calcium, the label states the drug works inside muscle cells "without altering serum calcium concentrations", so it does not deplete blood calcium and we found no human study showing calcium supplements blunt it. On heart protection, the 7,665-patient ACTION trial concluded: "Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival." Worse, with the old short-acting capsules, "the use of short-acting nifedipine in moderate to high doses causes an increase in total mortality." It relieves symptoms and lowers blood pressure; that is a different claim from protecting the heart.

Questions and answers

What is it?

Nifedipine is a synthetic tablet or capsule medicine in the dihydropyridine calcium channel blocker family. It blocks the channels that let calcium into heart muscle and artery wall muscle, so those muscles relax. It exists in a short-acting form and a 24-hour extended-release form built as a tiny osmotic pump, and the two behave differently enough that the safety evidence is not interchangeable. (Source 1)

What does it do in the body?

By keeping calcium out of the muscle in artery walls, it lets those arteries widen, so blood pressure falls and the heart meets less resistance. It also widens the coronary arteries and is a strong blocker of coronary spasm, which is why it helps the type of angina caused by spasm. It does not change the calcium level in your blood. (Source 20)

Is it good or bad for you?

It depends heavily on formulation and on what it is being used for. The long-acting form performed as well as a diuretic combination in a 6,321-patient hypertension trial, and lowering blood pressure is itself known to reduce strokes and heart attacks. But it did not improve survival or event rates when added to angina treatment, and the old short-acting capsules increased deaths in coronary disease in a dose-dependent way, reaching a risk ratio of 2.83 at 80 mg a day. Ankle swelling is common at any dose. (Source 2)

How do you get more of it?

It is prescription-only and the dose is chosen by a prescriber, not by the reader. As a matter of record, the extended-release labelling starts at 30 or 60 mg once daily, titrated over one to two weeks against blood pressure. The extended-release tablet has to be swallowed whole; breaking or chewing it defeats the osmotic pump that makes it long-acting. Nothing in food or any supplement supplies it. (Source 13)

If it is harmful, what reduces it?

If the drug itself needs to come down, that is a prescriber's decision, made by dose adjustment against blood pressure rather than abruptly. Two practical things do change exposure: avoiding grapefruit and grapefruit juice, which roughly doubles blood levels, and being aware that enzyme-inducing drugs cut levels sharply. Note that with the extended-release tablet the empty shell passes out in the stool, which is normal and not a sign the dose was lost. (Source 8)

Why might someone be low in it or missing it?

Nobody is deficient in nifedipine; it is a medicine, not a nutrient. Someone may be taken off it, or given less benefit from it, for three sorts of reason: side effects, chiefly ankle swelling, which caused an 8% excess of withdrawals in INSIGHT compared with a diuretic combination; interactions with enzyme-inducing drugs that cut blood levels by around 70%; or a decision that a different class suits them better. (Source 2)

Which whole foods contain it or feed it?

No food contains nifedipine. The food that matters is grapefruit, and it matters in the wrong direction: grapefruit juice inhibits the enzyme that clears the drug and roughly doubles exposure, so the labelling says to avoid it. A crossover study in 16 volunteers also found the juice delayed stomach emptying by about half an hour, producing a second peak in blood levels. (Source 7)

We searched: We searched Europe PMC for nifedipine food-source and food-effect studies and read the FDA PROCARDIA XL labelling sections on grapefruit juice and other interactions. Nifedipine is a synthetic dihydropyridine with no dietary source.

What happens if you do not have it?

Nothing happens from the absence of the drug itself. What returns is the condition. For high blood pressure the risk that treatment was reducing comes back: the labelling notes that lowering blood pressure reduces fatal and non-fatal cardiovascular events, mainly strokes and heart attacks. For vasospastic angina the spasm-driven chest pain can return. For stable angina, honestly, the trial evidence says stopping it does not change your risk of death or heart attack, only symptoms and procedure rates. (Source 21)

How can you test for it?

There is no blood test for nifedipine in normal care. The measurement that matters is blood pressure, which is how the dose is titrated, and symptom frequency for angina or Raynaud attacks. The labelling asks specifically for careful blood pressure monitoring during starting and dose increases, and more so in people already on other blood-pressure-lowering drugs. (Source 11)

References

1. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - prescribing information. 2026. Read the source
2. Lancet (London, England). Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). 2000. PMID 10972368, DOI 10.1016/s0140-6736(00)02527-7. Read the source
3. Lancet (London, England). Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. 2004. PMID 15351192, DOI 10.1016/s0140-6736(04)16980-8. Read the source
4. The Cochrane database of systematic reviews. Calcium channel blockers for inhibiting preterm labour and birth. 2014. PMID 24901312, DOI 10.1002/14651858.cd002255.pub2. Read the source
5. Rheumatology (Oxford, England). Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis. 2005. PMID 15546967, DOI 10.1093/rheumatology/keh390. Read the source
6. The New England journal of medicine. Prevention of high-altitude pulmonary edema by nifedipine. 1991. PMID 1922223, DOI 10.1056/NEJM199110313251805. Read the source
7. Journal of clinical pharmacy and therapeutics. Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms. 2005. PMID 15811168, DOI 10.1111/j.1365-2710.2004.00618.x. Read the source
8. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - warnings, adverse reactions, interactions and dosage sections. 2026. Read the source
9. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - warnings, adverse reactions, interactions and dosage sections. 2026. Read the source
10. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - drug interactions section (cimetidine and other interactions). 2026. Read the source
11. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - dosage and administration, blood pressure monitoring and adverse reaction rate sections. 2026. Read the source
12. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - warnings, adverse reactions, interactions and dosage sections. 2026. Read the source
13. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - dosage and administration, blood pressure monitoring and adverse reaction rate sections. 2026. Read the source
14. Circulation. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. 1995. PMID 7648682, DOI 10.1161/01.CIR.92.5.1326. Read the source
15. Circulation. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. 1995. PMID 7648682, DOI 10.1161/01.CIR.92.5.1326. Read the source
16. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - warnings, adverse reactions, interactions and dosage sections. 2026. Read the source
17. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - dosage and administration, blood pressure monitoring and adverse reaction rate sections. 2026. Read the source
18. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - warnings, adverse reactions, interactions and dosage sections. 2026. Read the source
19. The Cochrane database of systematic reviews. Calcium channel blockers for inhibiting preterm labour and birth. 2014. PMID 24901312, DOI 10.1002/14651858.cd002255.pub2. Read the source
20. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - prescribing information. 2026. Read the source
21. DailyMed / Pfizer Laboratories Div Pfizer Inc (FDA label). PROCARDIA XL (nifedipine) extended release tablets - prescribing information. 2026. Read the source