Amlostatin 5

Amlostatin 5

Pharmacodynamic properties
- Amlodipine belongs to a group called calcium channal blockers, with mainly 
  vascular effects.
- Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow 
  channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of 
  calcium ions into cardiac and vascular smooth muscle.
- The mechanism of the antihypertensive action of amlodipine is due to a direct 
   relaxant effect on vascular smooth muscle.
- Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral 
  resistance (afterload) against which the heart works. Since the heart rate remains 
  stable, this unloading of the heart reduces myocardial energy consumption and 
  oxygen requirements.
- The mechanism of action of amlodipine also probably involves dilatation of the main 
  coronary arteries and coronary arterioles, both in normal and ischaemic regions. This 
  dilatation increases myocardial oxygen delivery in patients with coronary artery 
  spasm (Prinzmetal's or variant angina).
- Amlodipine has not been associated with any adverse metabolic effects or changes in 
  plasma lipids and is suitable for use in patients with asthma, diabetes, and gout. 
Pharmacokinetic properties
- After oral administration of therapeutic doses, amlodipine is completely absorbed. 
  Absolute bioavailability has been estimated to be between 64 and 80%. Peak serum 
  concentration occurs late approximately 6 to 12 hours after dosing. The 
  bioavailability of amlodipine is not affected by food intake.
- The volume of distribution is approximately 21 l/kg. In vitro studies have shown that 
  approximately 97.5% of circulating amlodipine is bound to plasma proteins.
- Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% 
  of the parent compound and 60% of metabolites excreted in the urine.The terminal 
  plasma elimination half life is about 35 to 50 hours and is consistent with once daily 

Each tablet of Amlostatin® 5 contains: 
   Amlodipine 5 mg (As Amlodipine besylate ).
- Each tablet of Amlostatin® 10 contains: 
  Amlodipine 10 mg (As Amlodipine besylate ).

Amlostatin® is contraindicated in patients with:
- Hypersensitivity to dihydropyridine derivatives, amlodipine or to any of the    
- Severe hypotension.
- Shock (including cardiogenic shock).
- Obstruction of the outflow tract of the left ventricle (e.g., high grade aortic stenosis).
- Haemodynamically unstable heart failure after acute myocardial infarction.
- Have unstable angina

Effects of other medicinal products on amlodipine
- CYP3A4 inhibitors
  Concomitant use of Amlostatin®  with strong or moderate CYP3A4 inhibitors (protease 
  inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin,
  verapamil or diltiazem) may give rise to significant increase in amlodipine exposure 
  resulting in an increased risk of hypotension. The clinical translation of these PK 
  variations may be more pronounced in the elderly. Clinical monitoring and dose
  adjustment may thus be required.
- CYP3A4 inducers
  There is no data available regarding the effect of CYP3A4 inducers on amlodipine. 
  The concomitant use of CYP3A4 inducers (e.g., rifampicin, hypericum perforatum) 
  may give a lower plasma concentration of amlodipine. Amlodipine should be used 
  with caution together with CYP3A4 inducers. Administration of amlodipine with 
  grapefruit or grapefruit juice is not recommended as bioavailability may be increased 
  in some patients resulting in increased blood pressure lowering effects.

- Dantrolene (infusion)
  In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in 
  association with hyperkalemia after administration of verapamil and intravenous 
  dantrolene. Due to risk of hyperkalemia, it is recommended that the 
  coadministration of calcium channel blockers such as amlodipine be avoided in 
  patients susceptible to malignant hyperthermia and in the management of malignant 
Effects of amlodipine on other medicinal products
  The blood pressure lowering effects of amlodipine adds to the blood pressure-
  lowering effects of other medicinal products with antihypertensiveproperties.
  There is a risk of increased tacrolimus blood levels when coadministered with 
  amlodipine but the pharmacokinetic mechanism of this interaction is not fully 
  understood. In order to avoid toxicity of tacrolimus, administration of amlodipine in a 
  patient treated with tacrolimus requires monitoring of tacrolimus blood levels and dose 
  adjustment of tacrolimus when appropriate.
- Cyclosporine
  No drug interaction studies have been conducted with cyclosporine and amlodipine in 
  healthy volunteers or other populations with the exception of renal transplant patients, 
  where variable through concentration increases (average 0% 40%) of cyclosporine 
  were observed. Consideration should be given for monitoring cyclosporine levels in
  renal transplant patients on amlodipine, and cyclosporine dose reductions should be
  made as necessary.
- Simvastatin
  Coadministration of multiple doses of 10 mg of Amlostatin® with 80 mg simvastatin 
  resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. 
  Limit the dose of simvastatin in patients on amlodipine to 20 mg daily. In clinical 
  interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin,
  digoxin or warfarin.

No information available in pregnant women. Amlostatin® should be used during 
  pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Amlostatin® should not be used during lactation, no information available. 

Effects on ability to drive and use machines:
- If patients taking amlodipine suffer from dizziness, fatigue. Caution is recommended 
  especially at the start of treatment.

Somnolence, dizziness, headache (especially at the beginning of the treatment),visual 
  disturbance (including diplopia), palpitations, flushing, dyspnoea, abdominal pain, 
  nausea, dyspepsia, altered bowel habits (including diarrhoea and constipation), ankle 
  swelling, muscle cramps, fatigue, asthenia.
- Depression, mood changes (including anxiety), insomnia, tremor, dysgeusia, syncope, 
  hypoaesthesia, paraesthesia, tinnitus, arrhythmia (including bradycardia, ventricular 
  tachycardia and atrial fibrillation), hypotension, cough, rhinitis, vomiting, dry mouth, 
  alopecia, purpura, skin discolouration, hyperhidrosis, rash, exanthema, urticaria, 
  pruritus, arthralgia, myalgia, back pain, micturition disorder, nocturia, increased 
  urinary frequency, impotence, gynaecomastia, chest pain, pain, malaise, weight 
  increased, weight decreased.
- ou can report side effects directly via the:
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Patients with cardiac failure:
  Calcium channel blockers, including amlodipine, should be used with caution in 
  patients with congestive heart failure, as they may increase the risk of future 
  cardiovascular events and mortality.
- Patients with hepatic impairment: 
  The half-life of amlodipine is prolonged and AUC values are higher in patient swith 
  impaired liver function; dosage recommendations have not been established.
  Amlostatin® should therefore be initiated at the lower end of the dosing range and
  caution should be used, both on initial treatment and when increasing the dose. Slow 
  dose titration and careful monitoring may be required in patients with severe hepatic 

Amlostatin® 5  tablets:Blister of 10 tablets, pack of two blisters.
- Amlostatin® 10 tablets:Blister of 10 tablets, pack of two blisters.

- Store at temperature below 25ºC