Amlodipine  is a potent calcium channel blocker used for the treatment of the following conditions:

• Symptomatic chronic stable angina
• Treatment of confirmed or suspected vasospastic angina
• Treatment of hypertension.
• Raynaud's phenomenon

• Amlodipine dose in chronic stable angina:
  • 5 to 10 mg orally once daily. Beta-blocker should be used as the first line anti-anginal agent. Amlodipine may be added to beta-blocker if symptoms of angina persist or the patient remains symptomatic despite using a beta-blocker.
• Vasospastic angina:
  • 5 to 10 mg orally once daily in combination with a nitrate.
• Hypertension:
  • Initiate therapy at a dose of 2.5 to 5 mg once daily to a maximum daily dose of 10 mg once daily. Amlodipine may be used as a monotherapy or in combination with other agents like thiazide diuretics and an ACE inhibitor or ARB.
• Amlodipine dose in Raynaud phenomenon:
  • 5 mg once daily to a maximum dose of 20 mg once daily.

Amlodipine dose in children with Hypertension:

• Children 1 - 5 years of age:
  • Initial doses of 0.05-0.1 mg/kg/day.
• Children and Adolescents 6 to 17 years of age:
  • 2.5 to 5 mg once daily.
  • Weight-based dosages may range from 0.06 mg/kg/day to a maximum dose of 0.34 mg/kg/day (not to exceed 10 mg/day)

Pregnancy Risk factor C

Amlodipine is not recommended for pregnant women. It crosses the placenta. Since maternal hypertension may be related to serious adverse outcomes, amlodipine may be used, especially if other agents cannot be used.

Amlodipine use during breastfeeding

Breast milk contains very little amlodipine. Negative neonatal outcomes have never been reported. Amlodipine can be used in conjunction with breastfeeding.

Renal dose :

Dosage adjustment in kidney disease and patients on hemodialysis is not required.

Dose in liver disease :

Patients with severe liver disease may require a lower initial dose i.e. 2.5 mg. The dose should be titrated very slowly. 

Common side effects of amlodipine:

• Cardiovascular:
  • Peripheral edema
• Respiratory:
  • Pulmonary edema
• Cardiovascular:
  • Palpitations and flushing
• Central nervous system:
  • Fatigue, dizziness, male sexual disorder, and drowsiness.
• Dermatologic:
  • Pruritus and skin rash
• Gastrointestinal:
  • Nausea, constipation and abdominal pain
• Neuromuscular & skeletal:
  • Muscle cramps and weakness.
• Respiratory:
  • Dyspnea

Contraindications to Amlodipine include:

• Allergy reactions to amlodipine and any component of the formulation
• Allergies to medicines from the same group.
• Severe hypotension (SBP less than 90mm Hg).

Warnings and Precautions

• Angina and Myocardial infarction:
  • In the absence of a beta-blocker, reflex tachycardia can occur. This may lead to angina or myocardial infarction.
• Peripheral edema
  • After 2 to 3 weeks, edema can be seen as the most common side effect.
• Aortic stenosis and hypertrophic cardiomyopathy:
  • Ischemia may occur in patients suffering from severe aortic narrowing. It may cause an increase in the afterload for patients with HCM. These patients should be cautious when using it.
• Heart failure:
  • Patients with heart disease and reduced ejection fraction should avoid calcium channel blockers other that amlodipine.

Amlodipine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

  Risk Factor C (Monitor therapy).
  Alfuzosin	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Alpha1-Blockers	May increase the hypotensive effects of Calcium Channel Blockers.
  Amphetamines	May decrease the antihypertensive effects of Antihypertensive Drugs.
  Antipsychotic Agents, Second Generation (Atypical)	Blood Pressure Lowering Agents can increase the hypotensive effects of Antipsychotic Agents (Second Gen [Atypical]).
  Aprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  ARIPiprazole	CYP3A4 Inhibitors, Weak, may increase serum levels of ARIPiprazole. Monitoring for increased aripiprazole-pharmacologic effects is important. Aripiprazole dosage adjustments may be necessary depending on the indication and/or concomitant therapy. For more information, consult the full interaction monograph.
  Atosiban	Atosiban's toxic/adverse effects may be exacerbated by calcium channel blockers. There may be an increase in the risk of pulmonary edema or dyspnea.
  Barbiturates	Calcium Channel Blockers may increase metabolism. Monitoring: Check for reduced therapeutic effects of calcium channel blocking drugs when used in conjunction with barbiturate therapy. Adjustments in calcium channel blocker dosage may be required. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital.
  Barbiturates	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Benperidol	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Bosentan	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
  Brigatinib	May decrease the antihypertensive effects of Antihypertensive Drugs. Brigatinib could increase the bradycardic effects of Antihypertensive Drugs.
  Brimonidine (Topical)	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Calcium Channel Blockers (Nondihydropyridine)	Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers, Nondihydropyridine, may increase serum Calcium Channel Blockers (Dihydropyridine).
  Calcium Salts	This may reduce the therapeutic effects of Calcium Channel Blockers.
  Clofazimine	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Clopidogrel	Clopidogrel's therapeutic effects may be diminished by calcium channel blockers
  CycloSPORINE Systemic	Calcium Channel Blockers (Dihydropyridine), may increase the serum level of CycloSPORINE Systemic. CycloSPORINE Systemic may raise the serum calcium channel blockers (Dihydropyridine) concentration.
  Moderate CYP3A4 Inducers	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
  Moderate CYP3A4 inhibitors	May increase serum AmLODIPine concentrations
  Strong CYP3A4 inhibitors	May increase serum AmLODIPine concentrations
  Dapoxetine	May increase the orthostatic hypotensive effects of Calcium Channel Blockers.
  Deferasirox	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
  Dexmethylphenidate	Antihypertensive agents may have a less therapeutic effect.
  Diazoxide	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Dofetilide	Dofetilide may be increased by CYP3A4 inhibitors (Weak).
  DULoxetine	DULoxetine may increase hypotension by lowering blood pressure.
  Duvelisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Efavirenz	Could lower serum calcium channel blockers.
  Flibanserin	Flibanserin may be increased by CYP3A4 inhibitors (Weak).
  Fluconazole	May increase serum calcium channel blockers.
  Fosaprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Fosnetupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Herbs (Hypertensive Properties)	May decrease the antihypertensive effects of Antihypertensive Drugs.
  Herbs (Hypotensive properties)	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
  Ivosidenib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
  Larotrectinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Levodopa-Containing Products	Blood Pressure Lowering Agents can increase the hypotensive effects of Levodopa -Containing Products.
  Lormetazepam	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Lovastatin	Lovastatin serum concentration may be increased by AmLODIPine
  Magnesium Salts	Calcium Channel Blockers can increase the toxic/adverse effects of Magnesium Salts. Magnesium Salts can increase the hypotensive effects of Calcium Channel Blockers.
  Melatonin	May decrease the antihypertensive effects of Calcium Channel Blockers, Dihydropyridine.
  Methylphenidate	May decrease the antihypertensive effects of Antihypertensive Drugs.
  Molsidomine	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Naftopidil	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Netupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Neuromuscular-Blocking Agents (Nondepolarizing)	Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).
  Nicergoline	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Nicorandil	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  NiMODipine	CYP3A4 Inhibitors, Weak may increase NiMODipine serum concentrations.
  Nitrogen	The hypotensive effects of Nitroprusside may be enhanced by blood pressure lowering agents.
  Palbociclib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Pentoxifylline	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Pholcodine	Pholcodine may increase hypotensive effects by lowering blood pressure.
  Phosphodiesterase 5 Inhibitors	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Prostacyclin Analogues	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  Quinagolide	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
  QuiNIDine	Calcium Channel Blockers (Dihydropyridine), may increase QuiNIDine's serum concentration. QuiNIDine could increase the serum calcium channel blockers (Dihydropyridine) concentration. Calcium Channel Blockers (Dihydropyridine), may lower QuiNIDine's serum concentration.
  Sarilumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
  Siltuximab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
  Simeprevir	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Tacrolimus (Systemic)	Calcium Channel Blockers (Dihydropyridine), may increase the serum concentrations of Tacrolimus.
  Tocilizumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
  Yohimbine	Antihypertensive agents may have a lower antihypertensive impact. Risk C: Monitor therap
  Risk Factor D (Regard therapy modification)
  Amifostine	Amifostine's hypotensive effects may be enhanced by blood pressure lowering agents. Treatment: Blood pressure lowering drugs should be stopped 24 hours before amifostine administration. Amifostine should be avoided if blood pressure lowering medication cannot be withheld.
  Antifungal Agents (Azole Derivatives, Systemic)	Itraconazole may increase the toxic/adverse effect of Calcium Channel Blockers. Itraconazole, in particular, may increase the inotropic negative effects of verapamil and diltiazem. Antifungal Agents (AzoleDerivatives Systemic) can decrease calcium channel blocker metabolism. Isavuconazonium and fluconazole likely have weaker effects than other Azoles. These are discussed in separate monographs. Management: It is strictly forbidden to use felodipine and nisoldipine simultaneously with itraconazole. Any combination of these drugs should be monitored regularly. Calcium channel blocker dose reductions may also be necessary. Exceptions: Fluconazole; Isavuconazonium Sulfate.
  Antihepaciviral Combination Products	May increase serum levels of Amlodipine. Management: Lower amlodipine dosage by at least half and monitor for elevated amlodipine effects (eg hypotension) when an antihepaciviral combo product is used.
  CarBAMazepine	Calcium channel blockers (Dihydropyridine) may increase metabolism. Treatment: Patients who are taking concomitant carbamazepine should consider dose adjustments for calcium channel blockers (CCB). Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine.
  Strong CYP3A4 Inducers	May increase metabolism of CYP3A4 substrates (High Risk with Inducers). Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling.
  Dabrafenib	High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects).
  Enzalutamide	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Avoid concurrent use of enzalutamide and CYP3A4 substrates with a narrow therapeutic index. You should exercise caution when using enzalutamide or any other CYP3A4 sub-substance.
  Fosphenytoin	Calcium Channel Blockers can increase serum levels of Fosphenytoin. Management: Check for phenytoin toxicity when using a calcium channel blocking agent (CCB), or decrease in phenytoin effects after CCB discontinuation. Monitor for decreased therapeutic effects of CCB. Nimodipine Canadian labeling contraindicates use with phenytoin.
  Lomitapide	Lomitapide may be increased by CYP3A4 inhibitors (Weak). Management: Patients taking lomitapide 5 mg/day can continue to take this dose. Patients who are taking lomitapide 10mg/day or more must reduce their lomitapide dosage by half. You can then adjust the lomitapide dose to 30 mg/day for adults.
  Lorlatinib	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences.
  Antibiotics with Macrolide	Calcium Channel Blockers may be less metabolically active. Management: Use a non-interacting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Azithromycin (Systemic); Fidaxomicin, Roxithromycin and Spiramycin are exceptions.
  MiFEPRIStone	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid dihydroergotamine and ergotamine.
  Mitotane	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates.
  Obinutuzumab	This may increase the hypotensive effects of Blood Pressure Lowering Agents. Management: You may temporarily withhold blood pressure lowering medication beginning 12 hours before obinutuzumab injection and continuing for 1 hour after infusion.
  Phenytoin	Calcium Channel Blockers can increase the serum level of Phenytoin. The serum calcium channel blockers may be decreased by Phenytoin. Management: Phenytoin should not be used in combination with nimodipine and nifedipine. Monitoring for phenytoin toxicities and/or decreased calcium channel blocking effects is important with any concurrent use.
  Pitolisant	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrat with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances.
  Rifamycin Derivatives	This may cause a decrease in serum calcium channel blockers. This is primarily a problem with oral calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling.
  Simvastatin	Simvastatin may be increased by AmLODIPine. Simvastatin and amlodipine should not be used together. Simvastatin should not be taken together (for adults) in doses greater than 20 mg per day
  Sincalide	Sincalide may be less effective if drugs that affect gallbladder function are taken. Management: Before Sincalide is used to stimulate the gallbladder, discontinue any drugs that affect gallbladder motility.
  St John's Wort	High risk of Inducers causing a decrease in serum CYP3A4 Substrates. Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling.
  Stiripentol	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done.
  Risk Factor X (Avoid Combination)
  Bromperidol	Bromperidol's hypotensive effects may be enhanced by Blood Pressure Lowering agents. Bromperidol could decrease the hypotensive effects of Blood Pressure Lowering agents.
  Conivaptan	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Fusidic Acid (Systemic).	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Idelalisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
  Pimozide	Pimozide may be increased by CYP3A4 inhibitors (Weak).

Monitoring prameters :

Monitor the heart rate and blood pressure and titrate the dose upwards till the target blood pressure is achieved or the maximum dose is reached.

Administration :

Amlodipine may be taken without regards to meals.

Mechanism of action of Amlodipine:

Amlodipine prevents calcium ions entering the "slow channel" of the vascular smooth muscle during depolarization. This causes relaxation of the coronary smooth muscle (and coronary blood flow). Patients with vasospastic gina will experience an increase in oxygen delivery to their myocardium.

It also works directly on the smooth muscle of the vascular artery to cause peripheral arterial vasodilation, which reduces peripheral resistance and blood pressure. The onset of action is about 24 to 48 hours. The duration of action varies from 24 to 72 hours. It is well absorbed and is 93% protein bound.

Metabolism is mainly via the liver and the bioavailability varies from 64 to 90%. Half-life elimination varies from 30 to 50 hours and is prolonged in patients with hepatic impairment. The time to peak plasma concentration is around 6 to 12 hours Excretion is mainly via Urine.   

International brands :

• A-B Vask
• Actapin
• Adipin
• Aforbes
• Agen
• Aladin
• Alopine
• Alozur
• Amaday
• Ambesyl
• Amcal
• Amcard
• Amdepin
• Amdhapine
• Amdipin
• Amdixal
• Amedin
• Amilo
• Amlate
• Amlibon
• Amlibon BES
• Amlo-H10
• Amlo-H5
• Amlo-M
• Amlober
• Amloc
• Amlocar
• Amlocard
• Amlocor
• Amlodac
• Amlodar
• Amlode
• Amlodigamma
• Amlodin
• Amlodine
• Amlodno
• Amloget
• Amlogrix
• Amlong
• Amlopine
• Amlopres
• Amlopress
• Amlor
• Amlorine
• Amlostar
• Amlosyn
• Amlotan
• Amlotens
• Amlotrene
• Amlovasc
• Amlovasc 5
• Amlow
• Amlozen
• Amodin
• Amodipin
• Amopress
• Ampliron
• Amtas
• Amvasc
• Amze
• An Nei
• Zhen
• Anoldin
• Anydipine
• Ao Wan Lu
• Arainno
• Asomex-5.0
• Astudal
• Avevasc
• Avistar
• Awar
• Bezam
• Cab
• Calbloc
• Calchek
• Calvase
• Cardilopin
• Cardol
• Cobisk
• Cordarene
• Covasc
• CP-Lovac
• Cydipin
• DAILYvasc
• Deten
• Dipsope
• Du.Q
• Duactin 5
• Ertensi
• Evasc
• Fulopin
• Gensia
• Gravask
• Hovasc
• Istin
• Istolde
• Konipid
• Lama
• Licodipin
• Lodibes
• Lodip
• Lodipam
• Lofral
• Lomanor
• Lotense
• Lowdipine
• Lowrac
• Lowvasc
• Lupin
• Narvin
• Nexus
• Noloten
• Nopidin
• Nor-Lodipina
• Nordip
• Normodipine
• Norvapine
• Norvas
• Norvasc
• Norvasc ODT
• Norvask
• Novaspin
• Odasyl
• Opivask
• Prelod
• Presilam
• Provasc
• Remedopin S
• Sinnorvapin
• Sinop
• Sistopress
• Stadovas
• Stamlo
• Stamlo-10
• Tenox
• Tensiblat
• Terloc
• Varodipine
• Vascodipine
• Vascor
• Vasocal
• Vasotop
• Vasten
• Zynor
• ACCEL-Amlodipine
• ACT Amlodipine
• AG-Amlodipine
• APO-Amlodipine
• Auro-Amlodipine
• BIO-Amlodipine
• DOM-Amlodipine
• GD-Amlodipine
• JAMP-Amlodipine
• M-Amlodipine
• Mar-Amlodipine
• MINT-Amlodipine
• MYLAN-Amlodipine
• Norvasc
• NRA-Amlodipine
• PHARMA-Amlodipine
• PHL-Amlodipine
• PMS-Amlodipine
• Priva-Amlodipine
• Q-Amlodipine
• RAN-Amlodipine
• SANDOZ Amlodipine
• Septa-Amlodipine
• TEVA-Amlodipine
• VAN-Amlodipine

Brands in pakistan :