Nisoldipine (C20H24N2O6) is an FDA-approved 1,4-dihydropyridine calcium-channel blocker for the management of hypertension. The drug may be used alone or in combination with other antihypertensive agents (i.e., ACE-inhibitors, diuretics or beta-blockers). Off-label, nisoldipine may be used for the treatment of certain ischemic heart conditions such as stable angina or prinzmetal angina. The medication is also safe and effective for use in the geriatric population. However, drug safety and efficacy in the pediatric population and pregnant women remain unestablished.
Nisoldipine falls under the class of dihydropyridine calcium channel blockers. The drug acts on the systemic smooth muscle cells by inhibiting the influx of calcium by blocking the voltage-gated calcium channels located on the cells — the reduction in the calcium results in the dilation of coronary and systemic arteries.
Nisoldipine exhibits both antihypertensive and anti-anginal activity due to its ability to reduce systemic blood pressure and the myocardial oxygen demand (thereby increasing myocardial oxygen delivery to cells). This action ultimately results in vasodilation and decreases peripheral vascular resistance. The drug does not manifest any changes in the serum calcium concentrations and is insoluble in water.
Nisoldipine is available as an oral formulation as an extended-release tablet or as an extended-release hydrogel. The patient should take the medication on an empty stomach or an hour after meals. The drug is to be swallowed whole with water and not crushed or divided. The dosing adjustments recommendations are on weekly intervals based on patient response. Avoid grapefruit juice and high fat-meals with the medication administration due to their effect on drug bioavailability.
For ischemic heart conditions:
Patients with hepatic impairment:
Though nisoldipine is a well-tolerated medication among patients, it does have some side effects mainly associated with its vasodilating property. Common adverse effects associated with nisoldipine include flushing, hypotension, syncope, peripheral edema, headache, dizziness, and nausea. Additionally, chest pain, palpitations, dermatitis, pharyngitis, and sinusitis may also exhibit in individuals taking nisoldipine. Conditions such as anemia, anxiety, alopecia, difficulty swallowing, gingival hyperplasia, or ischemia are associated with less than 1% of the population taking the drug. Studies have shown that the abrupt withdrawal of nisoldipine may result in chest palpitations, chest pain, or increased severity of angina or hypertension. Thus the medication must be slowly tapered over time.
Nisoldipine is contraindicated in individuals with hypersensitivity to the drug or other dihydropyridine calcium channel blockers.
Caution is necessary for the elderly population due to higher drug plasma concentrations; recommendations are to start at a lower dose for safety. Extreme caution is necessary for patients with aortic stenosis, myocardial infarction, or hypotension due to the risk of reflex tachycardia resulting in the possible exacerbation of angina or worsening of myocardial infarction (MI). Though rare, patients with coronary artery disease may have increased frequency or severity of angina when starting nisoldipine. Safety measures are advised in patients with heart failure or left ventricular dysfunction and severe bradycardia due to the drug's hypotensive effect.
Breastfeeding women should avoid this drug due to the risk of excretion into breast milk. Due to the lack of well-controlled studies, pregnant women should avoid drug use to prevent any teratogenicity. Avoid concurrent use with cytochrome P450 inducers and inhibitors. Nisoldipine is also contraindicated with grapefruit products and high-fat meals (i.e., cheese, white bread, fried potatoes) due to its effect on absorption. Individuals diagnosed with GERD or a hiatal hernia should exercise caution when using nisoldipine due to its action on the esophageal sphincter.
Individuals taking nisoldipine should undergo monitoring for the relief of symptoms and any adverse effects pertaining to the medication. The patient's blood pressure should be carefully observed during each clinic visit and at home. It is also essential to monitor the cardiac function (i.e., heart rate) for any abnormalities at each physician visit, and dose adjustments made accordingly. It is also crucial to taper the dose slowly and make adjustments on weekly intervals. Liver function (LFTs) monitoring is a requirement in individuals with hepatic impairment. No dose adjustments are necessary for renal impairment.
Toxicity due to nisoldipine has its basis in clinical status and history. As described above, hypotension, coupled with reflex tachycardia, can present when patients take an overdose on dihydropyridine calcium channel blockers such as nisoldipine. In some severe cases of nisoldipine toxicity, the clinician will note hypotension with bradycardia. Secondary findings of confusion, heart failure, and abnormal ECG changes such as PR prolongation can be indicative. Additionally, hyperglycemia in patients without diabetes can suggest calcium channel blockers poisoning.
If toxicity is suspected, resuscitation is a priority. IV fluids and atropine for bradycardia are necessary alongside frequent reassessments by clinical staff. If a patient presents with severe symptoms, maintaining the airway, IV isotonic crystalloid, calcium salts, glucagon, insulin, and vasopressor therapy are all viable options and usable collectively. Activated charcoal should be administered in all patients suspected of nisoldipine overdose.
An interprofessional team is the optimal means by which to successfully manage patients treated with dihydropyridine calcium channel blockers such as nisoldipine. Providers must be knowledgable regarding the symptoms of toxicity. To improve clinical outcomes, a team consisting of nurses, laboratory technicians, pharmacists, physicians, and other healthcare professionals are necessary to optimize care. Pharmacists should offer to consult about the use of glucagon, insulin, and vasopressor therapy. A toxicologist consult should also take place when indicated. Cardiologists, intensivists, and the emergency team may have involvement in managing a patient further as many of these cases require further interventional management during the hospital course, including maintenance of an airway. By coordinating care, a patient on nisoldipine who may be experiencing toxicity or adverse symptoms can have successful management.
Interprofessional team dynamics will also serve to prevent nisoldipine toxicity. The prescriber can consult a pharmacist, who will verify dosing and check the medication record for potential drug interactions. Nursing will be able to perform much of the monitoring necessary at follow-up visits, as well as helping determine patient compliance and treatment effectiveness. Both the pharmacist and nursing should alert the prescriber to any concerns promptly, so adjustments to the regimen (either dosing or agent selection) can be made and lead to improved patient outcomes. [Level 5]
|||Nisoldipine 2006; [PubMed PMID: 30000110]|
|||Thadani U,Zellner SR,Glasser S,Bittar N,Montoro R,Miller AB,Chaitman B,Schulman P,Stahl A,DiBianco R, Double-blind, dose-response, placebo-controlled multicenter study of nisoldipine. A new second-generation calcium channel blocker in angina pectoris. Circulation. 1991 Dec; [PubMed PMID: 1959195]|
|||Chen YH,Liu RC,Wang SP, Antianginal and anti-ischemic efficacy of nisoldipine in stable angina pectoris: a randomized, double-blind, placebo-controlled trial. Zhonghua yi xue za zhi = Chinese medical journal; Free China ed. 1996 Nov; [PubMed PMID: 9037847]|
|||Kim S,Yu YM,Kwon J,Yoo H,Jung SH,Lee E, Calcium Channel Blocker-Associated Chyloperitoneum in Patients Receiving Peritoneal Dialysis: A Systematic Review. International journal of environmental research and public health. 2019 Apr 13; [PubMed PMID: 31013922]|
|||Dudhipala N,Veerabrahma K, Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug development and industrial pharmacy. 2015; [PubMed PMID: 25830370]|
|||Dudhipala N,Janga KY,Gorre T, Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation. Artificial cells, nanomedicine, and biotechnology. 2018; [PubMed PMID: 29688077]|
|||Rameis H, [Principles of the pharmacokinetics and pharmacodynamics of calcium antagonists]. Wiener medizinische Wochenschrift (1946). 1993; [PubMed PMID: 8135031]|
|||Tajani AH,Nesbitt SD, Gingival hyperplasia in a patient with hypertension. Journal of clinical hypertension (Greenwich, Conn.). 2008 Nov; [PubMed PMID: 19128276]|
|||Ikemura N,Yamaori S,Kobayashi C,Kamijo S,Murayama N,Yamazaki H,Ohmori S, Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chemico-biological interactions. 2019 Jun 1; [PubMed PMID: 30965050]|
|||Bailey DG,Dresser GK, Interactions between grapefruit juice and cardiovascular drugs. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2004; [PubMed PMID: 15449971]|
|||St-Onge M,Dubé PA,Gosselin S,Guimont C,Godwin J,Archambault PM,Chauny JM,Frenette AJ,Darveau M,Le Sage N,Poitras J,Provencher J,Juurlink DN,Blais R, Treatment for calcium channel blocker poisoning: a systematic review. Clinical toxicology (Philadelphia, Pa.). 2014 Nov; [PubMed PMID: 25283255]|
|||White WB,Saunders E,Noveck RJ,Ferdinand K, Comparative efficacy and safety of nisoldipine extended-release (ER) and amlodipine (CESNA-III study) in African American patients with hypertension. American journal of hypertension. 2003 Sep; [PubMed PMID: 12944032]|
|||Lenz TL,Wurdeman RL,Hilleman DE, Comparison of 24-hour blood pressure profiles in patients with hypertension who were switched from amlodipine to nisoldipine. Pharmacotherapy. 2001 Aug; [PubMed PMID: 11718496]|
|||Wachowiak R,Strach B,Lopatka P, [Toxicological analysis of selected 1,4-dihydropyridine calcium channel blockers in the diagnosis of intoxications]. Archiwum medycyny sadowej i kryminologii. 2005 Jan-Mar; [PubMed PMID: 15984121]|