Levamlodipine
JFDA label: conjupri
Mechanism of Action
12.1 Mechanism of Action Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Amlodipine is a 1:1 racemic mixture of levamlodipine and dextro amlodipine, it has been demonstrated that levamlodipine is the pharmacologically active, anti-hypertensive isomer.
Indications
Approved
- Cardiovascular Diseases — cardiovascular disease
Off-label
- Hypertension
Contraindications
Source: openFDA
- Levamlodipine is contraindicated in patients with known sensitivity to amlodipine. Known sensitivity to amlodipine. ( 4 ) Absolute
Dosing
Source: openFDA
Warnings & Precautions
Source: openFDA
Warnings & Precautions
Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely. ( 5.1 ) Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. ( 5.2 ) Titrate slowly in patients with severe hepatic impairment. ( 5.3 )
Hypotension Symptomatic hypotension is possible, particularly in patie
Hypotension Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.
Increased Angina or Myocardial Infarction Worsening angina and acute m
Increased Angina or Myocardial Infarction Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
Patients with Hepatic Failure Because amlodipine is extensively metabo
Patients with Hepatic Failure Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t 1/2 ) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.
Chemistry & Properties
| Formula | C20H25ClN2O5 |
|---|---|
| Molecular weight | 408.88 g/mol |
| IUPAC name | 3-O-ethyl 5-O-methyl (4S)-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate |
| CAS | 103129-82-4 |
| PubChem CID | 9822750 |
| InChIKey | HTIQEAQVCYTUBX-KRWDZBQOSA-N |
| logP | 2.27 (XLogP 3.0) |
| Polar surface area | 99.88 Ų |
| H-bond acceptors / donors | 7 / 2 |
| Drug-likeness (QED) | 0.50 |
| Lipinski violations | 0 |
SMILES
CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)[C@@H]1c1ccccc1ClBiology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 10.0% |
|---|---|
| Half-life | 0.541 h |
| Volume of distribution | 23.032 L/kg |
| Protein binding | 96.7% |
| BBB penetrant | No |
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2B6 | Inhibitor | — |
| CYP2C8 | Inhibitor | — |
| CYP3A4 | Inhibitor | — |
| CYP3A4 | Substrate | — |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Apalutamide | major | |
| Ceritinib | major | |
| Dolasetron | major | |
| Enzalutamide | major | |
| Lumacaftor | major | |
| Mitotane | major | |
| Simvastatin | major | |
| Siponimod | major | |
| Acalabrutinib | moderate | |
| Acetylsalicylic acid | moderate | |
| Adalimumab | moderate | |
| Aldesleukin | moderate | |
| Alefacept | moderate | |
| Alimemazine | moderate | |
| Amifostine | moderate | |
| Anakinra | moderate | |
| Apixaban | moderate | |
| Aprepitant | moderate | |
| Axitinib | moderate | |
| Betamethasone | moderate | |
| Bexarotene | moderate | |
| Bosutinib | moderate | |
| Brigatinib | moderate | |
| Brimonidine (ophthalmic) | moderate | |
| Brimonidine (topical) | moderate | |
| Budesonide | moderate | |
| Bupropion | moderate | |
| Calcium Phosphate | moderate | |
| Calcium acetate | moderate | |
| Calcium carbonate | moderate | |
| Calcium chloride | moderate | |
| Calcium citrate | moderate | |
| Calcium glubionate anhydrous | moderate | |
| Calcium glucoheptonate | moderate | |
| Calcium gluconate | moderate | |
| Calcium lactate | moderate | |
| Canagliflozin | moderate | |
| Canakinumab | moderate | |
| Certolizumab pegol | moderate | |
| Chloramphenicol | moderate |
Showing 40 of 100+.
Registered Products (2)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| conjupri | Tablet 2.5 mg | 30 tab pack varies | moon light drugs store | 5.020 |
| conjupri | Tablet 2.5 mg | 90 tab pack varies | moon light drugs store | 12.970 |