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Levamlodipine

Medically reviewed by Drugs.com. Last updated on Nov 19, 2020.

Pronunciation

(lev am LOE di peen)

Index Terms

  • Conjupri
  • Gloperba
  • Levamlodipine Maleate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as maleate:

Conjupri: 2.5 mg, 5 mg [scored]

Brand Names: U.S.

  • Conjupri

Pharmacologic Category

  • Antihypertensive
  • Calcium Channel Blocker
  • Calcium Channel Blocker, Dihydropyridine

Pharmacology

Amlodipine is a 1:1 racemic mixture of levamlodipine and dextro amlodipine; it has been demonstrated that levamlodipine is the pharmacologically active, antihypertensive isomer. Amlodipine is a dihydropyridine calcium channel blocker that exerts its effect by blocking the transmembrane influx of calcium ions primarily into vascular smooth muscle cells and to a lesser extent into cardiac muscle cells. It reduces peripheral vascular resistance and lowers BP by acting directly on vascular smooth muscle.

Metabolism

Hepatic (~90%) to inactive metabolites.

Excretion

Urine (10% of total dose as unchanged drug, 60% of total dose as metabolites).

Clearance: May be decreased in patients with hepatic insufficiency or moderate to severe heart failure; weight-adjusted clearance in children >6 years of age is similar to adults.

Onset of Action

Gradual.

Time to Peak

6 to 12 hours.

Duration of Action

≥24 hours.

Half-Life Elimination

Terminal (biphasic): ~30 to 50 hours; increased with hepatic dysfunction.

Protein Binding

~93%.

Special Populations: Hepatic Function Impairment

AUC may increase ~40% to 60%.

Special Populations: Elderly

AUC may increase ~40% to 60%.

Special Populations Note

Moderate to severe heart failure: AUC may increase ~40% to 60%.

Use: Labeled Indications

Hypertension: Treatment of hypertension, alone or in combination with other antihypertensive agents, in adults and pediatric patients ≥6 years of age.

Contraindications

Hypersensitivity to levamlodipine, amlodipine, or any component of the formulation.

Dosing: Adult

Hypertension:

Note: For initial treatment in patients with BP ≥20/10 mm Hg above goal, may be used in combination with another appropriate agent (eg, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, thiazide diuretic). For patients <20/10 mm Hg above goal, some experts recommend an initial trial of monotherapy; however, over time, many patients will require combination therapy (ACC/AHA [Whelton 2018]; Mann 2019).

Oral: Initial: 1.25 to 2.5 mg once daily; titrate every 1 to 2 weeks as needed based on patient response; maximum: 5 mg/day. Antihypertensive effect attenuates with higher doses and adverse effects may become more prominent (Mann 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Note: Dosing should start at the lower end of dosing range and be titrated to response due to possible increased incidence of hepatic, renal, or cardiac impairment. Elderly patients also show decreased clearance of amlodipine.

Hypertension: Oral: Initial: 1.25 mg once daily.

Dosing: Pediatric

Hypertension: Children and Adolescents 6 to ≤17 years: Oral: 1.25 to 2.5 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: May be administered without regard to food.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Consider therapy modification

Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Consider therapy modification

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy

CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Levamlodipine. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Levamlodipine. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy

Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Calcium Channel Blockers may decrease the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Consider therapy modification

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Lovastatin: Levamlodipine may increase the serum concentration of Lovastatin. Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Consider therapy modification

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Consider therapy modification

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers (CCBs) contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. If coadministered, monitor for decreased CCB efficiacy. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simvastatin: Levamlodipine may increase the serum concentration of Simvastatin. Management: Dose of simvastatin should not exceed 20 mg daily if coadministering with levamlodipine or amlodipine. If coadministering with simvastatin and levamlodipine, close laboratory and clincal monitoring for signs and symptoms of rhabdomyolysis is warranted. Consider therapy modification

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Test Interactions

May lead to false-negative aldosterone/renin ratio (Funder 2016).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. All adverse reactions were reported with amlodipine, as levamlodipine is the pharmacologically active isomer of amlodipine.

>10%: Cardiovascular: Peripheral edema (2% to 11% [placebo: <0.6%], dose-related; females: 15% [placebo: 5%]; males: 6% [placebo: 1%])

1% to 10%:

Cardiovascular: Flushing (≤3%; dose-related, more frequent in females), palpitations (1% to 5%; dose-related, more frequent in females)

Gastrointestinal: Abdominal pain (2%), nausea (3%)

Nervous system: Dizziness (doses ≥5 mg/day: 3%), drowsiness (1%), fatigue (5%)

<1%:

Cardiovascular: Peripheral ischemia, sinus tachycardia, syncope, vasculitis

Dermatologic: Diaphoresis, erythema multiforme, pruritus, skin rash

Endocrine & metabolic: Hot flash, hyperglycemia, weight gain, weight loss

Gastrointestinal: Anorexia, constipation, dysphagia, flatulence, gingival hyperplasia, pancreatitis, vomiting, xerostomia

Genitourinary: Nocturia, urinary frequency

Hematologic & oncologic: Leukopenia, purpuric disease, thrombocytopenia (Cvetković 2013)

Hypersensitivity: Angioedema, hypersensitivity reaction

Nervous system: Abnormal dreams, anxiety, depersonalization, depression, female sexual disorder, hypoesthesia, insomnia, malaise, male sexual disorder, pain, paresthesia, peripheral neuropathy, rigors, vertigo

Neuromuscular & skeletal: Arthralgia, arthropathy, asthenia, back pain, muscle cramps, myalgia, tremor

Ophthalmic: Conjunctivitis, diplopia, eye pain

Otic: Tinnitus

Respiratory: Dyspnea, epistaxis

Postmarketing:

Dermatologic: Dermatologic disorder (Schamberg's disease) (Schetz 2015), toxic epidermal necrolysis (Baetz 2011)

Endocrine and metabolic: Gynecomastia (Cornes 2001)

Hepatic: Cholestatic hepatitis (Egbuonu 2019; Zinsser 2004), hepatotoxicity (Demirci 2013; Hammerstrom 2015)

Renal: Acute interstitial nephritis (Ejaz 2000)

Warnings/Precautions

Concerns related to adverse effects:

• Angina/myocardial infarction: Increased angina and/or myocardial infarction (MI) have occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur, resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade.

• Hypotension: Symptomatic hypotension can occur; acute hypotension upon initiation is unlikely due to the gradual onset of action. BP must be lowered at a rate appropriate for the patient's clinical condition.

• Peripheral edema: The most common side effect is peripheral edema; occurs within 2 to 3 weeks of starting therapy.

Disease-related concerns:

• Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may cause hypotension or reduce coronary perfusion, resulting in ischemia.

• Heart failure: Calcium channel blockers should be avoided whenever possible in patients with heart failure with reduced ejection fraction (ACCF/AHA [Yancy 2013]).

• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose; titrate slowly in patients with severe hepatic impairment.

• Hypertrophic cardiomyopathy with outflow tract obstruction: Use amlodipine with caution in patients with hypertrophic cardiomyopathy and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (ACCF/AHA [Gersh 2011]).

Special populations:

• Elderly: Initiate at a lower dose in elderly patients.

Other warnings/precautions:

• Titration: Peak antihypertensive effect is delayed; dosage titration should occur after 7 to 14 days on a given dose.

Monitoring Parameters

Heart rate, BP.

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2018]):

Confirmed hypertension and known cardiovascular disease or 10-year atherosclerotic cardiovascular disease risk ≥10%: Target BP <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased atherosclerotic cardiovascular disease risk: Target BP <130/80 mm Hg may be reasonable.

Diabetes and hypertension: The American Diabetes Association guidelines (ADA 2020):

Patients 18 to 65 years of age, without atherosclerotic cardiovascular disease, and 10-year atherosclerotic cardiovascular disease risk <15%: Target BP <140/90 mm Hg is recommended.

Patients 18 to 65 years of age and known atherosclerotic cardiovascular disease or 10-year atherosclerotic cardiovascular disease risk ≥15%: Target BP <130/80 mm Hg may be appropriate if it can be safely attained.

Patients >65 years of age (healthy or complex/intermediate health): Target BP <140/90 mm Hg is recommended.

Patients >65 years of age (very complex/poor health): Target BP <150/90 mm Hg is recommended.

Pregnancy Considerations

Amlodipine is a racemic mixture of levamlodipine and dextro amlodipine; levamlodipine is the pharmacologically active isomer. Amlodipine crosses the placenta (Morgan 2017; Morgan 2018).

Refer to the amlodipine monograph for additional information,

Patient Education

What is this drug used for?

• It is used to treat high blood pressure.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Loss of strength of energy

• Flushing

• Nausea

• Abdominal pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• Severe dizziness

• Passing out

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Swelling

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.