PDP-AMLODIPINE

1 Dosing Considerations Dosing should be individualized depending on patient’s tolerance and responsiveness. 2 Recommended Dose and Dosage Adjustment For both hypertension and angina, the recommended initial dose of pdp-AMLODIPINE (amlodipine besylate) is 5 mg (5 mL) once daily.

If necessary, dose can be increased after 1-2 weeks to a maximum of 10 mg (10 mL) once daily.

Geriatrics (≥ 65 years of age):

The recommended initial dose in patients over 65 years of age is 5 mg (5 mL) once daily. If required, increasing in the dose should be done gradually and with caution (See WARNINGS AND PRECAUTIONS).

Patients with Impaired Renal Function:

The recommended initial dose in patients with impaired renal function is 5 mg (5 mL) once daily. If required, increasing in the dose should be done gradually and with caution (See ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).

Patients with Impaired Hepatic Function:

Dosage requirements have not been established in patients with impaired hepatic function (mild, moderate or severe). When pdp-AMLODIPINE is used in these patients, the dosage should be carefully and gradually adjusted depending on the patient’s tolerance and response.

5 mL) once daily should be considered (See WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic). 5 mL) to 5 mg (5 mL) once daily. Doses in excess of 5 mg (5 mL) daily have not been studied; dose should be determined based upon the medical need of the patients.

In children, gender differences in blood pressure response to amlodipine have been observed (See WARNINGS AND PRECAUTIONS and ACTION AND CLINICAL PHARMACOLOGY). 3 Administration pdp-AMLODIPINE is for oral administration. This product should not be shaken prior to administration.

, with breakfast, lunch or at bedtime), but it should not be mixed with food or beverages before use. 4 Missed Dose If a dose is missed, it should be taken as soon as the patient remembers. If it has been more than 12 hours since the last dose, the missed dose should be skipped and the next dose can be continued at the regular time.

1 Adverse Reaction Overview Amlodipine besylate has been administered to 1,714 patients (805 hypertensive and 909 angina patients) in controlled clinical trials (vs placebo alone and with active comparative agents). Most adverse reactions reported during therapy were of mild to moderate severity.

2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. 9% of patients. 3%). 5%). 7%). 5%). 5%). 7%). 4%). 5%). 5%). 6% of patients. 8%). 6%). 8%). 0%). 9%). 9%). 7%). 9%). 1%).

6%). 0%). 3 Less Common Clinical Trial Adverse Reactions Amlodipine besylate has been evaluated for safety in about 11,000 patients with hypertension and angina. 1% of patients in comparative clinical trials (double-blind comparative vs placebo or active agents; n = 2,615) or under conditions of open trials or marketing experience where a causal relationship is uncertain.

Autonomic Nervous System: dry mouth, hyperhidrosis. Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, myocardial infarction, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis, chest pain.

Central and Peripheral Nervous System: hypoaesthesia/paraesthesia, neuropathy peripheral, tremor, vertigo. Gastrointestinal: anorexia, constipation, dysphagia, vomiting, gingival hyperplasia, change in bowel habits, dyspepsia General: allergic reaction, asthenia+, back pain, pain, hot flushes, malaise, rigors, and weight increased/weight decreased.

General Beta-blocker Withdrawal: pdp-AMLODIPINE (amlodipine besylate) gives no protection against the dangers of abrupt beta-blocker withdrawal and such withdrawal should be done by the gradual reduction of the dose of beta-blocker.

Peripheral Edema:

Mild to moderate peripheral edema was the most common adverse event in the clinical trials (See ADVERSE REACTIONS). 8% in 5 to 10 mg dose range. Care should be taken to differentiate this peripheral edema from the effects of increasing left ventricular dysfunction.

Concomitant Use with Strong Inhibitors of CYP 3A4:

Use of pdp-AMLODIPINE with drugs that result in strong inhibition of CYP 3A4, such as ketoconazole, clarithromycin, ritonavir, may lead to increased plasma levels of amlodipine and associated serious events (See DRUG INTERACTIONS).

Such concomitant use should be avoided. I. 02)]. (See DRUG INTERACTIONS).

Effects of Glycerol Intake:

Glycerol is a non-medicinal ingredient used in the pdp- AMLODIPINE oral solution formulation. Before initiating treatment with pdp-AMLODIPINE, the patient should be informed that this drug contains glycerol which may cause gastro-intestinal discomfort, laxative effects and headaches in some patients, particularly in children.

The use of pdp-AMLODIPINE is contraindicated in patients with hyperglycerolemia or glycerol kinase deficiency (See CONTRAINDICATIONS).

Cardiovascular Increased Angina and/or Myocardial Infarction:

Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase.

pdp-AMLODIPINE is contraindicated in patients:  Who are hypersensitive to this drug or to any ingredient in the formulation, including any pdp-AMLODIPINE Product Monograph Page 4 of 35 non-medicinal ingredient, or component of the container.

For a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.  With hypersensitivity to other dihydropyridines* (See DRUG INTERACTIONS). )  With severe hypotension (less than 90 mmHg systolic). )  Who are nursing women, as amlodipine is transferred into human breast milk (See WARNINGS AND PRECAUTIONS).

 With hereditary fructose intolerance (See WARNINGS AND PRECAUTIONS).  With hyperglycerolemia or glycerol kinase deficiency (See WARNINGS AND PRECAUTIONS, General, Effects of Glycerol Intake).