Nifedipine & Lercanidipine: Evidence, Oedema and Pregnancy

Table of contents

• Evidence summary
• What these medicines are
• How they work
• What they are prescribed for
• What works and what does not
• Benefits by claim
• Risks and all side effects
• All interactions
• Who should avoid them
• Dosage and how to take them
• Follow the money: who makes them and who funded the evidence
• Related research
• Frequently asked questions
• Sources and funding notes

Evidence summary

Independent evidence and credibility scorecard

Independence tiers: 1 = regulator or government body; 2 = academic or Cochrane team with no declared commercial funding for the work; 3 = independent authors, but the funder is unconfirmed or the product or topic is closely tied to a manufacturer; 4 = manufacturer-funded or manufacturer-authored. Credibility runs from A (highest) to D. All twelve sources are listed; most come from the UK and Europe, so the evidence reflects European practice and European drug brands.

What these medicines are

All three are dihydropyridine calcium channel blockers, like amlodipine. This article covers the ones other than amlodipine.

• Nifedipine: the oldest. It was developed by Bayer, which holds the original patent on the slow-release tablet (assignee Bayer AG; priority date 9 September 1980) (EP0047899B2). Bayer’s brand is Adalat. In the UK, Adalat LA is licensed to Bayer plc (Adalat LA SmPC). In the US, the once-daily osmotic tablet is Procardia XL, labelled by Pfizer (DailyMed). The label also describes an older capsule form, which was tested separately.
• Lercanidipine: a newer drug that Recordati says it discovered and developed in its own laboratories (Recordati 2025 accounts). The brand is Zanidip. UK generics exist, such as a tablet licensed to Mylan (Viatris) (SmPC).
• Felodipine: sold as generic extended-release tablets of 2.5, 5 and 10 mg in the US. The label we used is from PAR Health (DailyMed). Recordati also sells a metoprolol and felodipine combination (Logimax) (Recordati 2025 accounts).

“GITS” and “modified-release” matter. The big nifedipine trials used a once-daily GITS tablet (30 mg in INSIGHT, 60 mg in ACTION) (INSIGHT; ACTION). The mortality warning from 1995 concerned short-acting nifedipine, so the two should not be mixed up (Furberg 1995). Both the US and UK labels say the modified-release tablets must be swallowed whole (FDA label; Adalat LA SmPC).

How they work

The US label describes nifedipine as a “calcium ion influx inhibitor” that acts on vascular smooth muscle (FDA label). Blocking calcium entry relaxes artery walls and lowers blood pressure. That blood-pressure effect is proven in humans: in INSIGHT, average pressure fell from 173/99 to 138/82 mm Hg (Brown 2000). Lercanidipine is described by its maker as a “latest-generation” calcium channel blocker (Recordati); its UK label gives the same use, mild to moderate essential hypertension (SmPC).

What is not established is why the drugs help in Raynaud’s. The Cochrane review of primary Raynaud’s found that five trials measured physiological outcomes and saw no significant differences (Ennis 2016). So the symptom benefit is shown, but a clear vessel-level explanation is not.

What it is prescribed for

• Nifedipine (US): vasospastic angina, chronic stable angina in people who remain symptomatic on beta-blockers or nitrates (or cannot tolerate them), and hypertension (FDA label).
• Nifedipine (UK, Adalat LA): hypertension, and prophylaxis of chronic stable angina alone or with a beta-blocker (SmPC).
• Lercanidipine: mild to moderate essential hypertension in adults (SmPC).
• Felodipine: hypertension (label).
• Off-label uses seen in practice: Raynaud’s phenomenon and hypertension in pregnancy. Neither is on the labels we read, but both have trial evidence and, for pregnancy, a NICE recommendation (see below).

Where these drugs sit in adult hypertension care: NICE says to offer a calcium channel blocker as first treatment to adults aged 55 or over without type 2 diabetes, and to Black African or African-Caribbean adults of any age without type 2 diabetes. If a calcium channel blocker is not tolerated, for example because of oedema, NICE says to offer a thiazide-like diuretic (NICE NG136). The recommendations name no individual calcium channel blocker. See also our guides to hypertension and blood pressure medicines.

What works and what does not

Benefits by claim

Does nifedipine protect the heart?

In INSIGHT, 6,321 adults aged 55 to 80 with hypertension and at least one extra risk factor took nifedipine GITS 30 mg (3,157 people) or co-amilozide, a diuretic mix (3,164 people). Major events occurred in 200 (6.3%) and 182 (5.8%) people (RR 1.10, 95% CI 0.91 to 1.34, p=0.35). Serious adverse events were less frequent on nifedipine (796 vs 880, p=0.02), but more people stopped it for oedema (725 vs 518, p<0.0001) (Brown et al. 2000). In plain English: both drugs worked equally well on events, and the trade-off was swelling versus other side effects.

In ACTION, people with stable angina already on treatment were given nifedipine GITS 60 mg (3,825) or placebo (3,840) and followed for 4.9 years. Deaths were 1.64 vs 1.53 per 100 patient-years (HR 1.07, 95% CI 0.91 to 1.25). The combined endpoint did not change (HR 0.97, 95% CI 0.88 to 1.07). Death plus any cardiovascular event or procedure fell (HR 0.89, 95% CI 0.83 to 0.95), mainly through fewer coronary angiographies and interventions, despite more peripheral revascularisation (Poole-Wilson et al. 2004). The trial abstract reports no effect on heart attack rates, and the ACC summary reports that study drug was permanently discontinued in 34% of the nifedipine group and 31% of the placebo group stopping treatment (ACC). Because Bayer paid for ACTION, we treat its safety message (“safe”) as the maker-funded conclusion of a well-run trial, not independent proof.

Are lercanidipine and felodipine as good?

Lercanidipine has strong blood-pressure data but no outcome trial, and a systematic review found no basis for calling it equivalent to nifedipine GITS, whose 24-hour effect looked more consistent (Elliott and Meredith 2014). For felodipine we reviewed only the label, which describes use for hypertension (label). Felodipine was the baseline drug in the large HOT trial of blood pressure targets (18,790 people), but its funding is not shown in the PubMed record we opened, so we cite it as context only (Hansson et al. 1998).

Lercanidipine versus amlodipine: ankle swelling

The most-cited comparison is the COHORT double-blind trial. In 828 people aged 60 or over, followed for about 12 months, oedema was reported by 19% on amlodipine 5 mg, 9% on lercanidipine 10 mg and 4% on lacidipine 2 mg (P<.001). Stopping early for oedema was 8.5%, 2.1% and 1.4%. Blood pressure fell comparably in all three, and other side effects did not differ (Leonetti et al. 2002).

A 2009 meta-analysis of eight trials agrees: oedema in 52 of 742 people on lercanidipine vs 88 of 627 on amlodipine, felodipine or nifedipine (RR 0.44, 95% CI 0.31 to 0.62), and withdrawal for oedema was lower (RR 0.24, 95% CI 0.12 to 0.47). Blood pressure control did not differ, and there was no difference against second-generation drugs (Makarounas-Kirchmann et al. 2009). Elliott and Meredith’s review of lercanidipine against nifedipine GITS estimated oedema at about 2.5 per 100 patients on lercanidipine against 6 per 100 on nifedipine GITS, with 99.5 and 98 to 99 per 100 still on treatment, respectively (Elliott 2014). A fair reading: lercanidipine probably swells ankles less than amlodipine, but the sources are not clearly independent of its maker, and it does not remove the problem. NICE advises a diuretic if a calcium channel blocker is not tolerated (NG136). See also our guide to swollen ankles.

Hypertension in pregnancy

NICE NG133 recommends the following. For chronic hypertension: “Consider labetalol”, then nifedipine for women in whom labetalol is not suitable, then methyldopa (1.3.10). For gestational hypertension, the same order (1.4.5). For pre-eclampsia, NICE uses stronger wording: “Offer labetalol”, then nifedipine where labetalol is unsuitable (1.5.6). Treatment is offered to women with chronic hypertension who are not yet on treatment if pressure is sustained at 140/90 mm Hg or higher, with a target of 135/85 mm Hg (1.3.8, 1.3.9). For severe hypertension in critical care, NICE lists oral nifedipine alongside labetalol and intravenous hydralazine (1.8.6) (NICE NG133). So nifedipine is a recognised choice, but it is not the first one.

Why labetalol first? The evidence does not separate them. For very high blood pressure, calcium channel blockers beat hydralazine (persistent high blood pressure 8% vs 22%; RR 0.37, 95% CI 0.21 to 0.66; 6 trials, 313 women), and the Cochrane authors said the choice should rest on clinician experience, known adverse effects and the woman’s preference (Duley et al. 2013). A 2016 meta-analysis of 7 small trials (363 women) found oral nifedipine had less persistent hypertension than intravenous labetalol, but the result was not significant on sensitivity analysis (Shekhar et al.). A 2025 network meta-analysis of 23 trials (3,989 women) found a modest edge for labetalol over nifedipine on pre-eclampsia (RR 0.50, 95% CI 0.28 to 0.87) and preterm birth (RR 0.68, 95% CI 0.52 to 0.90), with no difference in severe hypertension and low-to-moderate quality evidence (Hup et al.). The Giant PANDA trial plans to randomise 2,300 women to nifedipine or labetalol, with NIHR funding (protocol); we found no published results.

Labels add a wrinkle. NICE notes that some nifedipine brands were contraindicated in pregnancy by their manufacturers when the guideline was published, and tells prescribers to check each product (NICE NG133). The UK Adalat LA label says not to use it in pregnancy unless the woman’s clinical condition requires nifedipine (SmPC). The lercanidipine label says it is not recommended in pregnancy (SmPC). See also heart disease during pregnancy.

Raynaud’s phenomenon

The 2016 Cochrane review of primary Raynaud’s found 7 trials with 296 people (four tested nifedipine, the rest nicardipine). Attack frequency fell by 1.72 attacks per week (95% CI 0.60 to 2.84; SMD 0.23, 95% CI 0.08 to 0.38). Severity differed little. In one trial, 73% of people on nifedipine reported improvement vs 33% on placebo (P<0.001). Reviewers called the benefit minimal (Ennis et al. 2016). The 2017 review of primary and secondary Raynaud’s (38 trials, 982 people, average 7.4 weeks) found fewer attacks (about 3 to 6 a week depending on how one outlying trial was handled), a 0.62 cm drop on a 10 cm severity scale, and no serious adverse events, with most data coming from nifedipine (Rirash et al. 2017). Both reviews rely on small, short trials. See our guide to Raynaud phenomenon.

Risks and all side effects

We found no boxed warning in the nifedipine and felodipine label text we read, but the text was partly truncated, so check the full labels.

Common side effects

Gum overgrowth (gingival hyperplasia)

The felodipine label tells prescribers to warn patients that mild gingival hyperplasia (gum swelling) has been reported (label). The lercanidipine label lists gingival hypertrophy as a post-marketing report (SmPC), and the Adalat LA label lists gingival hyperplasia among gastrointestinal effects (SmPC). In a community study of 911 people in northeast England, 6.3% of 442 nifedipine users had significant overgrowth, higher than amlodipine (181 users) or diltiazem (186 users), which were not significantly different from 102 controls. Men were about three times as likely as women to be affected, and gum inflammation was a cofactor. Earlier studies had reported 20% to 83% (Ellis et al. 1999). Good tooth cleaning and dental review are sensible, but that is common advice, not a finding of this study.

All interactions

• Grapefruit juice: about doubled nifedipine AUC and peak (the label advises avoiding it) (FDA label); more than doubled felodipine exposure (label); contraindicated with lercanidipine (SmPC). The UK Adalat LA label says the effect can persist for at least three days after the last grapefruit juice (SmPC).
• CYP3A4 inhibitors: fluconazole, itraconazole and clarithromycin may raise nifedipine exposure (FDA label). Felodipine’s label lists ketoconazole, itraconazole, erythromycin and cimetidine (label). Ketoconazole raised lercanidipine AUC about 15-fold, and strong inhibitors, ciclosporin and grapefruit are contraindicated (SmPC).
• CYP3A4 inducers: phenytoin lowered nifedipine exposure by about 70%, and the label says to avoid it or any known inducer (FDA label; Pfizer). Adalat LA must not be combined with rifampicin (SmPC). Anticonvulsants markedly reduce felodipine exposure (label).
• Beta-blockers: usually well tolerated with nifedipine, but may increase the chance of heart failure, severe hypotension or worse angina (FDA label). Metoprolol roughly halved lercanidipine bioavailability (SmPC). See bisoprolol.
• Digoxin: levels should be monitored when starting, changing or stopping nifedipine (FDA label); lercanidipine raised digoxin peak by a mean 33% (SmPC).
• Simvastatin: AUC rose 56% with lercanidipine, probably not clinically relevant per the label (SmPC).
• Magnesium sulfate in pregnancy: the UK label asks for close blood-pressure monitoring when nifedipine is used with intravenous magnesium sulfate (SmPC).
• Alcohol: the lercanidipine label advises avoiding it (SmPC).
• Supplements: see our guide to supplements and heart medicines.

Who should avoid them

• Adalat LA is contraindicated in inflammatory bowel disease or Crohn’s disease, with rifampicin, in cardiogenic shock, significant aortic stenosis, unstable angina, within one month of a heart attack, and with a Kock pouch or gastrointestinal obstruction (SmPC).
• Lercanidipine is contraindicated in left ventricular outflow obstruction, untreated congestive heart failure, unstable angina or a heart attack in the past month, severe liver impairment, severe kidney impairment (GFR below 30 ml/min), and with strong CYP3A4 inhibitors, ciclosporin or grapefruit (SmPC).
• Liver disease: people with cirrhosis have a longer half-life and higher bioavailability of nifedipine (FDA label); impaired liver function should start felodipine at 2.5 mg (label).
• Pregnancy: see above. The US nifedipine and felodipine labels say there are no adequate, well-controlled studies in pregnant women; the felodipine label reports digit anomalies in rabbit fetuses (FDA label; label).
• Breastfeeding: the Adalat LA label says breastfed infants receive a small fraction of the maternal dose and that infants should be watched for low blood pressure (SmPC). The lercanidipine label says not to use it while breastfeeding (SmPC). NICE recommends enalapril for postnatal hypertension, and for women of Black African or Caribbean family origin suggests nifedipine or amlodipine if previously effective (1.9.4, 1.9.5) (NICE NG133).

Dosage and how to take them

These are label and trial doses, not advice.

• Adalat LA (UK): a starting dose of one 20 mg tablet daily for mild to moderate hypertension, 30 mg daily for severe hypertension and angina, a maximum of 90 mg once daily, swallowed whole (SmPC).
• Procardia XL (US): starting at 30 or 60 mg once daily, with titration over 7 to 14 days. Above 120 mg is not recommended for hypertension, and experience above 90 mg in angina is limited (Pfizer dosing).
• Lercanidipine (UK): 10 mg once daily at least 15 minutes before meals, which may be raised to 20 mg (SmPC).
• Felodipine (US): 2.5 to 10 mg once daily in the trials cited by the label (label).
• Trial doses: nifedipine GITS 30 mg (INSIGHT) and 60 mg (ACTION); lercanidipine 10 mg and amlodipine 5 mg (COHORT) (INSIGHT; ACTION; COHORT).
• Product quality: NICE tells prescribers to check each nifedipine product’s SmPC, because pregnancy wording differed between brands (NICE NG133). We found no regulator recall notice for these drugs in the sources we could open.

Follow the money: who makes them and who funded the evidence

Who made them, and who sells them now

• Nifedipine (Bayer, Germany): Bayer AG is the assignee of the original slow-release tablet patent, filed 28 August 1981 with a German priority date of 9 September 1980 (Google Patents record). Bayer is headquartered in Leverkusen, Germany, and is listed in Frankfurt (Wikipedia, secondary source). In the UK, Adalat LA is licensed to Bayer plc (SmPC). In the US, Procardia XL is labelled by Pfizer (DailyMed). A Wikipedia history, which we treat as secondary, says a court found Pfizer’s Procardia XL was also based on Bayer’s patents (Wikipedia: Nifedipine); we could not verify that from a primary source.
• Lercanidipine (Recordati, Italy): Recordati is headquartered in Milan and listed on the Italian stock exchange (Recordati about us). Its 2025 accounts say lercanidipine was discovered and developed entirely in its laboratories and Zanidip is available in more than 60 countries. Zanidip together with Zanipress (lercanidipine plus enalapril) brought in €180.5 million in 2025 (€179.3 million in 2024), against group net revenue of €2,618.4 million, so roughly 7% of sales. The accounts also say it makes the active ingredient in a dedicated plant in Cork, Ireland (Recordati 2025 accounts). Its patent expiry in major European markets hit sales: they fell 30.8% to €148.7 million in 2010 (PharmaTimes, 2011).
• Felodipine: today sold by many generic makers in the US; the DailyMed search we ran listed PAR Health, Westminster Pharmaceuticals and Heritage (Avet) among others (label). Recordati also sells the metoprolol and felodipine combination Logimax; with Seloken it recorded €107.0 million in 2025 (Recordati 2025 accounts).

Who funded the trials

• ACTION (nifedipine GITS in angina): funded by Bayer Healthcare AG, Wuppertal, Germany, according to the paper’s acknowledgements as recorded by a university research portal (record). The European Society of Hypertension summary calls it investigator-initiated with an independent steering committee (ESH). Both can be true: investigators designed it and the maker paid.
• INSIGHT (nifedipine GITS in hypertension): we did not find a funding statement in the PubMed record, the Oxford Academic abstract page or a British Journal of Cardiology summary. One secondary source said Bayer sponsored it, but we could not open the paper’s own statement. Treat it as maker-linked until the acknowledgements are checked.
• Lercanidipine trials and meta-analysis: COHORT (2002) and the 2009 meta-analysis list no funder in PubMed. Recordati is the originator; the sponsor is unconfirmed (COHORT; 2009 meta-analysis).
• Public funders: the Cochrane pregnancy review was funded by the UK Department of Health and the Medical Research Council (Duley 2013); the Giant PANDA trial by NIHR (protocol); the 2016 Raynaud’s review by the UK Chief Scientist Office, though some authors report Actelion ties (Ennis 2016). Cochrane’s sponsorship policy bars for-profit sponsors with a stake in the findings from funding reviews (policy).

Documented integrity events

In 1995, a meta-analysis found higher mortality with high-dose short-acting nifedipine in coronary disease, a finding that reduced use of the drug and led to the focus on long-acting forms (Furberg 1995). Beyond that, we found no regulator warning letters, bans or fines for nifedipine, lercanidipine or felodipine in the sources we opened. The Bayer–Pfizer patent dispute noted above is a commercial matter, not a safety one, and we could not confirm it from primary sources.

Ownership and backers

Recordati says it is subject to management and coordination by Rossini Luxembourg S.à r.l. (Recordati), and its 2025 accounts say the immediate parent, Rossini S.à r.l. in Luxembourg, is owned by a consortium of investment funds controlled by CVC Capital Partners (Recordati 2025 accounts). Bayer’s shareholder register was not traced. We did not trace individual board members.

Related research

For wider, evidence-graded context, see these Pure City Research guides:

• Amlodipine: blood pressure and angina uses, swelling and safety
• Hypertension: accurate measurement, treatment, safety and evidence funding
• Blood pressure medicines: types, monitoring, side effects and safety
• Resistant hypertension
• High blood pressure: prevention and management evidence
• Stable angina
• Vasospastic angina
• Raynaud phenomenon
• Swollen ankles and legs
• Heart disease during pregnancy
• Bisoprolol
• Supplements and heart medicines: interactions

Frequently asked questions

Sources and funding notes

What we could not verify: (1) INSIGHT’s funder; (2) funding for COHORT, the 2009 lercanidipine meta-analysis, Elliott 2014, Shekhar 2016, Ellis 1999 and Furberg 1995, because no funding statement was visible in the records we opened; (3) the Bayer–Pfizer patent ruling, which comes only from Wikipedia; (4) whether Giant PANDA has reported; (5) the full text of the NICE and felodipine documents beyond the sections we quote (the felodipine text we read was truncated); and (6) felodipine outcome trials, which we did not review beyond the label. The HOT trial used felodipine as baseline therapy (PubMed), but its funding is not in the record we opened. Wikipedia pages are secondary sources, used for ownership and history only. Lercanidipine’s US status was not checked.

1. NICE NG133: Hypertension in pregnancy — UK guideline (published 25 June 2019, last updated 17 April 2023); funded via NICE, a body sponsored by the Department of Health and Social Care. Read through an archived copy because the live page blocked automated access.
2. NICE NG136: Hypertension in adults — UK guideline; same funder. Archived copy.
3. GOV.UK: National Institute for Health and Care Excellence — UK government; confirms NICE’s sponsor.
4. Procardia XL label, DailyMed — FDA-approved text written by Pfizer. Text we read was truncated.
5. Pfizer Medical: Procardia XL precautions and dosage and administration — manufacturer-hosted label text.
6. Felodipine extended-release label, DailyMed (PAR Health) — FDA-approved generic label.
7. Adalat LA 30 mg SmPC, emc — MHRA-approved; licence holder Bayer plc; revised 12 May 2026.
8. Lercanidipine 10 mg SmPC, emc (Mylan/Viatris) — MHRA-approved generic text; revised 14 December 2020 per its section 10.
9. Brown et al., INSIGHT, Lancet 2000 — trial; funder not confirmed.
10. Poole-Wilson et al., ACTION, Lancet 2004 — trial; funded by Bayer Healthcare AG per university portal record. Also ACC summary and ESH summary.
11. Furberg, Psaty, Meyer, Circulation 1995 — meta-analysis; funder not found.
12. Leonetti et al., Am J Hypertens 2002 — trial; sponsor not stated in PubMed.
13. Makarounas-Kirchmann et al., Clin Ther 2009 — meta-analysis; funder not stated.
14. Elliott and Meredith, World J Cardiol 2014 — systematic review; funding not visible in the text we opened.
15. Duley et al., Cochrane 2013 — funded by UK Department of Health and MRC.
16. Shekhar et al., BJOG 2016 — meta-analysis; funder not stated.
17. Hup et al., Am J Obstet Gynecol 2025 — network meta-analysis; funded by a grant from Achmea, a Dutch health insurer, per the Europe PMC grant record.
18. Ashworth et al., Giant PANDA protocol, Trials 2023 — NIHR HTA funded.
19. Ennis et al., Cochrane 2016 — Raynaud’s; UK Chief Scientist Office grant.
20. Rirash et al., Cochrane 2017 — Raynaud’s; funding not shown in the record we opened.
21. Ellis, Seymour, Steele, J Periodontol 1999 — gum overgrowth; funder not stated.
22. Hansson et al., HOT trial, Lancet 1998 — context only; funder not stated.
23. Recordati Group integrated consolidated financial statements 2025 and Recordati about us — company documents.
24. PharmaTimes: Recordati battles through loss of lercanidipine patent — trade press, 10 February 2011.
25. Google Patents: EP0047899B2 — Bayer AG patent record.
26. Cochrane commercial sponsorship policy — Cochrane (UK).
27. Wikipedia: Nifedipine and Wikipedia: Bayer — secondary; history only; Bayer headquarters location.

Educational research reviewed 9 October 2026. This article is not medical advice; talk to a qualified clinician or pharmacist before starting, stopping or combining treatments.