Consumer medicine information

Amlodipine GH

Amlodipine

BRAND INFORMATION

Brand name

Amlodipine GH

Active ingredient

Amlodipine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amlodipine GH.

SUMMARY CMI

Amlodipine GH

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Amlodipine GH?

Amlodipine GH contains the active ingredient amlodipine besilate. Amlodipine GH is used to lower high blood pressure (hypertension) and treat angina pectoris. For more information, see Section 1. Why am I using Amlodipine GH? in the full CMI.

2. What should I know before I use Amlodipine GH?

Do not use if you have ever had an allergic reaction to amlodipine besilate or any of the ingredients listed at the end of the CMI. Talk to your doctor or pharmacist if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I use Amlodipine GH? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Amlodipine GH and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Amlodipine GH?

  • The usual dose of Amlodipine GH is one 5 mg tablet each day, although a 2.5 mg dose may be prescribed in some cases. Your doctor may increase this to one 10 mg tablet each day.
  • Your doctor may prescribe another dose of Amlodipine GH depending on your condition and how you respond to this medicine.
  • Swallow the tablet whole with a full glass of water. Amlodipine GH 5 mg tablets can be divided in half along the scoreline if your doctor has prescribed a 2.5 mg dose.

More instructions can be found in Section 4. How do I use Amlodipine GH? in the full CMI.

5. What should I know while using Amlodipine GH?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Amlodipine GH.
  • Avoid eating large quantities of grapefruit or drinking large quantities of grapefruit juice.
Things you should not do
  • Do not give Amlodipine GH to anyone else, even if they have the same condition as you.
  • Do not take Amlodipine GH to treat any other complaints unless your doctor tells you to.
Driving or using machines
  • Be careful driving or operating machinery until you know how this medicine affects you.
  • Amlodipine GH may cause dizziness or light-headedness in some people, especially after the first dose or after the dose has been increased. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Store Amlodipine GH tablets below 30°C. Protect from light.

For more information, see Section 5. What should I know while using Amlodipine GH? in the full CMI.

6. Are there any side effects?

Common side effects: headache, dizziness, flushing, tiredness, drowsiness or sleepiness, stomach pain or nausea. Serious side effects: changes in heart beat (fast or slow), swelling of the ankles, feet, face of hands, tingling or numbness of the hands or feet, muscle cramps or aches, changes in mood, feeling anxious or nervous.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Amlodipine GH

Active ingredient(s): amlodipine besilate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Amlodipine GH. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Amlodipine GH.

Where to find information in this leaflet:

1. Why am I using Amlodipine GH?
2. What should I know before I use Amlodipine GH?
3. What if I am taking other medicines?
4. How do I use Amlodipine GH?
5. What should I know while using Amlodipine GH?
6. Are there any side effects?
7. Product details

1. Why am I using Amlodipine GH?

Amlodipine GH contains the active ingredient amlodipine besilate. Amlodipine GH belongs to a group of medicines called calcium channel blockers or calcium ion antagonists. They work by widening your blood vessels, making it easier for your heart to pump blood around the body and help increase the supply of blood and oxygen to your heart. Calcium channel blockers do not change the amount of calcium in your blood or bones.

Amlodipine GH is used to:

  • lower high blood pressure (also known as hypertension). There are usually no symptoms of hypertension. The only way of knowing that you have hypertension is to have your blood pressure checked on a regular basis. If high blood pressure is not treated it can lead to serious health problems.
  • treat angina pectoris. Angina is a pain or uncomfortable feeling in the chest, often spreading to the arms or neck, and sometimes to the shoulders and back. The pain of angina is due to a shortage of oxygen to the heart. Amlodipine GH is not for the relief of a sudden attack of angina. If such an attack occurs, you should take other medication that your doctor will have given to you.

2. What should I know before I use Amlodipine GH?

Warnings

Do not use Amlodipine GH if:

  • you are allergic to amlodipine besilate or other medicines of this drug class (such as felodipine, nifedipine or lercanidipine), or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.
    Some of the symptoms of an allergic reaction may include:
    - shortness of breath, wheezing or difficulty breathing;
    - swelling of the face, lips, tongue or other parts of the body;
    - rash, itching or hives on the skin

Check with your doctor or pharmacist if you:

  • are pregnant or intend to become pregnant.
  • are breastfeeding.
  • have, or have had, any other medical conditions, including:
    - heart problems, including heart failure; or
    - liver problems.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor or pharmacist if you are pregnant or intend to become pregnant.

This medicine may affect your developing baby if you take it during pregnancy. Your doctor can discuss with you the risks and benefits involved.

Talk to your doctor or pharmacist if you are breastfeeding or intend to breastfeed.

The active ingredient in Amlodipine GH passes into breast milk. Your baby may be affected.

Use in children

There is not enough information to recommend the use of this medicine in children.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Amlodipine GH and affect how it works. This includes:

  • other medicines used to treat angina, such as diltiazem.
  • some antibiotics, such as erythromycin, clarithromycin or rifampicin.
  • some antifungals, such as ketoconazole or itraconazole.
  • anti-proteases, medicines used to treat HIV infection, such as ritonavir.
  • simvastatin, a medicine used to lower cholesterol.
  • ciclosporin, tacrolimus, sirolimus or everolimus, medicines used to suppress the immune system.
  • temsirolimus, a medicine used to treat kidney cancer.
  • St John's Wort.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Amlodipine GH.

4. How do I use Amlodipine GH?

How much to take

  • The usual dose of Amlodipine GH is one 5 mg tablet each day, although a 2.5 mg dose may be prescribed in some cases. Your doctor may increase this to one 10 mg tablet each day.
  • Your doctor may prescribe another dose of Amlodipine GH depending on your condition and how you respond to this medicine.

When to take Amlodipine GH

  • Amlodipine GH may be taken at any time of the day. However, take your tablet about the same time each day, either morning or evening. This will help you to get the best effect and also makes it easier to remember when to take it.
  • You must take Amlodipine GH every day.
  • Continue taking your medicine for as long as your doctor tells you.

How to take Amlodipine GH

  • Swallow the tablet with a full glass of water.
  • If you need to break Amlodipine GH, hold the tablet with both hands and snap along the break line.
  • Amlodipine GH can be taken with or without food.

If you forget to use Amlodipine GH

Amlodipine GH should be used regularly at the same time each day. If you miss a dose and it is less than 12 hours before your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then get back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed.

If you use too much Amlodipine GH

If you think that you have used too much Amlodipine GH, you may need urgent medical attention.

If you take too much Amlodipine GH, you may need urgent medical attention.

You may feel dizzy, light-headed or faint, or have an irregular heartbeat if you have taken too much Amlodipine GH.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26); or
  • contact your doctor; or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Amlodipine GH?

Things you should do

  • If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Amlodipine GH.
  • Keep all of your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Call your doctor straight away if you:

  • become pregnant while taking Amlodipine GH.

Remind any doctor, dentist or pharmacist you visit that you are using Amlodipine GH.

Things you should not do

  • Do not give Amlodipine GH to anyone else, even if they have the same condition as you.
  • Do not take Amlodipine GH to treat any other condition unless your doctor tells you to.
  • Avoid eating large quantities of grapefruit or drinking large quantities of grapefruit juice. Grapefruit juice contains one or more components that alter the metabolism of some medicines, including Amlodipine GH. Drinking very large quantities (over 1.2 litres) of grapefruit juice each day while taking Amlodipine GH may increase the effects of this medicine.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Amlodipine GH affects you.

Amlodipine GH may cause dizziness or light-headedness in some people, especially after the first dose or after the dose has been increased.

If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Self-help measures for high blood pressure or angina

Some self-help measures suggested below may assist your condition. Your doctor or pharmacist can give you more information about these measures:

  • Weight loss: Your doctor may suggest losing some weight. Some people may need a dietician to plan a suitable diet to help with weight loss.
  • Exercise: Regular exercise helps lower blood pressure and strengthen the heart. It is important not to overdo it. Before commencing regular exercise, you should consult your doctor who will suggest the most suitable exercise for you. If you feel uncomfortable when exercising or experience symptoms such as unusual chest pain or breathlessness, see your doctor.
  • Alcohol: Your doctor may advise you to limit your alcohol intake.
  • Salt: Your doctor may advise you to watch the amount of salt in your diet. To reduce your salt intake, you should avoid using salt at the table or in cooking.
  • Smoking: Your doctor may advise you to stop smoking or at least cut down.

Drinking alcohol

Tell your doctor if you drink alcohol. Your doctor may advise you to limit your alcohol intake.

Looking after your medicine

  • Keep your tablets in a cool dry place in the original packaging where temperatures stay below 30°C. Protect from light.
  • Keep your tablets in the blister pack until it is time to take them.

Follow the instructions on the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink; or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions.

If you are 65 years or older, you should be especially careful when you are taking Amlodipine GH.

Some people in this age group are more likely to experience side effects such as swelling of the feet and ankles, muscle cramps and dizziness.

Less serious side effects

Less serious side effectsWhat to do
General disorders:
  • Headache.
  • Dizziness.
  • Tiredness.
  • Drowsiness or sleepiness.
  • Dizziness or light-headedness when standing up from a sitting or lying position.
Gut or gastrointestinal-related:
  • Stomach pain or nausea.
  • Indigestion.
Others:
  • Sexual problems.
  • Flushing
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Muscle or joint-related:
  • Swelling of the ankles, feet, face or hands.
  • Tingling or numbness of the hands or feet.
  • Muscle cramps or aches.
  • Joint pain.
Brain-related:
  • Changes in mood, feeling anxious or nervous.
Liver-related:
  • itching, yellowing of the skin and eyes, and dark coloured urine.
Gut or gastrointestinal-related:
  • Severe upper stomach pain, often with nausea and vomiting.
Allergy-related:
  • Swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing.
  • Shortness of breath.
  • Symptoms of allergy such as skin rash and/or itching.
Heart-related:
  • Changes in heart beat (fast or slow).
  • Fast or irregular heart beat.
  • Chest pain.
  • Chest pain associated with exertion (angina) that lasts longer, is more severe or occurs more often.
Others:
  • Unusual tiredness or weakness.
  • Eye pain or change in vision.
  • Unusual movements, including trembling and shaking of the hands, and fingers, twisting movements of the body, shuffling walk and stiffness of the arms and legs.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Amlodipine GH contains

Active ingredient
(main ingredient)		Amlodipine besilate
Other ingredients
(inactive ingredients)		Microcrystalline cellulose
Mannitol
Sodium starch glycollate
Colloidal anhydrous silica
Magnesium stearate
Potential allergensNot applicable

Do not take this medicine if you are allergic to any of these ingredients.

Does not contain gluten, sugar or lactose.

What Amlodipine GH looks like

Amlodipine GH 5 mg is a white to off-white, octagonal-shaped, uncoated tablet debossed with ‘AM 5’ on one side and a scoreline on the other side (AUST R 140104).

Amlodipine GH 10 mg is a white to off-white, octagonal-shaped, uncoated tablet debossed with ‘AM 10’ on one side and plain on the other side (AUST R 140140).

Who distributes Amlodipine GH

Generic Health Pty Ltd
Suite 2, Level 2
19-23 Prospect Street
Box Hill, VIC, 3128
Australia

ii1076201  [email protected]

ii1076202  +61 3 9809 7900

ii1076203  www.generichealth.com.au

This leaflet was prepared in December 2024.

Published by MIMS March 2025

BRAND INFORMATION

Brand name

Amlodipine GH

Active ingredient

Amlodipine

Schedule

S4

 

1 Name of Medicine

Amlodipine besilate.

2 Qualitative and Quantitative Composition

Each tablet contains 5 mg or 10 mg amlodipine (as besilate).

List of excipients with known effects.

Mannitol.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Amlodipine GH 5 mg tablets: White to off-white, octagonal shaped, uncoated tablets, debossed with "AM 5" on one side and scoreline on the other side.
Amlodipine GH 10 mg tablets: White to off-white, octagonal shaped uncoated tablets, debossed with "AM 10" on one side and plain on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

1. Hypertension.

Amlodipine GH tablets are indicated for the first line treatment of hypertension and can be used as the sole agent to control blood pressure in the majority of patients. Patients not adequately controlled on a single antihypertensive agent may benefit from the addition of amlodipine, which has been used in combination with a thiazide diuretic, beta adrenoceptor blocking agent or an angiotensin converting enzyme (ACE) inhibitor.

2. Angina.

Amlodipine GH tablets are indicated for the first line treatment of chronic stable angina. Amlodipine GH tablets may be used alone, as monotherapy or in combination with other anti-anginal drugs.

4.2 Dose and Method of Administration

Dosage.

For hypertension or angina the usual initial dose is 2.5 mg to 5 mg once daily which may be increased to a maximum dose of 10 mg depending on the individual patient's response.

Method of administration.

Amlodipine tablets are for oral administration.

Dosage adjustment.

Small, fragile or elderly individuals, or patients with hepatic insufficiency should be started on 2.5 mg once daily and this dose may be used when adding amlodipine tablets to other antihypertensive therapy.
Amlodipine GH 5 mg tablets can be divided in half along the scoreline if your doctor has prescribed a 2.5 mg dose.
Dosage should be adjusted according to each patient's need. In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient's response to each dose level. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently. See Section 4.8 Adverse Effects (Undesirable Effects) for information related to dosage and adverse effects.

Co-administration with other antihypertensive and/or anti-anginal drugs.

Amlodipine tablets have been safely administered with thiazides, ACE inhibitors, beta-blockers, long acting nitrates, and/or sublingual nitroglycerin.
No dose adjustment of amlodipine tablets is required upon concomitant administration of thiazide diuretics, beta-blockers, long acting nitrates and ACE inhibitors.

4.3 Contraindications

Amlodipine GH tablets are contraindicated in patients with a known hypersensitivity to amlodipine, other dihydropyridines, or any of the inactive ingredients.

4.4 Special Warnings and Precautions for Use

Increased angina.

Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration and/or severity of angina on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.

Outflow obstruction (aortic stenosis).

Amlodipine GH tablets should be used with caution in the presence of a fixed left ventricular outflow obstruction (aortic stenosis).

Use in patients with congestive heart failure.

In general, calcium channel blockers should be used with caution in patients with heart failure. Amlodipine tablets (5 mg to 10 mg per day) have been studied in a placebo controlled trial of 1153 patients with NYHA class III or IV heart failure on stable doses of ACE inhibitor, digoxin and diuretics. Follow-up was at least 6 months, with a mean of about 14 months. There was no overall adverse effect on survival or cardiac morbidity (as defined by life threatening arrhythmia, acute myocardial infarction, or hospitalisation for worsened heart failure). Amlodipine tablets have been compared to placebo in four 8 to 12 week studies of patients with NYHA class II/III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or LVEF.

Beta-blocker withdrawal.

Amlodipine is not a beta-blocker and therefore provides no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of beta-blocker.

Peripheral oedema.

Mild to moderate peripheral oedema was the most common adverse event in the clinical trials (see Section 4.8 Adverse Effects (Undesirable Effects)). The incidence of peripheral oedema was dose dependent and ranged in frequency from 3.0% to 10.8% in the 5 mg to 10 mg dose range. Care should be taken to differentiate this peripheral oedema from the effects of increasing left ventricular dysfunction.

Use in hepatic impairment.

There are no adequate studies in patients with liver dysfunction and dosage recommendations have not been established. In a small number of patients with mild to moderate hepatic impairment given single doses of 5 mg, amlodipine half-life has been prolonged. Worsening of liver function test values may occur. Amlodipine GH tablets should, therefore, be administered with caution in these patients and careful monitoring should be performed. A lower starting dose may be required (see Section 4.2 Dose and Method of Administration).

Use in renal impairment.

Amlodipine is extensively metabolised to inactive metabolites with 10% excreted as unchanged drug in the urine. Changes in amlodipine plasma concentrations are not correlated with the degree of renal impairment. Amlodipine GH tablets may be used at normal doses in patients with renal failure. Amlodipine is not dialysable.

Use in the elderly.

In elderly patients (≥ 65 years) clearance of amlodipine is decreased with a resulting increase in AUC. In clinical trials the incidence of adverse events in elderly patients was approximately 6% higher than that of younger population (< 65 years). Adverse events include oedema, muscle cramps and dizziness. Amlodipine GH tablets should be used cautiously in elderly patients.

Paediatric use.

Safety and effectiveness have not been established in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Amlodipine tablets have been safely administered with thiazide diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, long acting nitrates, sublingual nitroglycerine, nonsteroidal anti-inflammatory drugs, antibiotics and oral hypoglycaemic drugs.
Special studies have indicated that the coadministration of amlodipine tablets with digoxin did not change serum digoxin levels or digoxin renal clearance in healthy volunteers, and that coadministration of cimetidine did not alter the pharmacokinetics of amlodipine; and that coadministration with warfarin did not change the warfarin prothrombin response time.
In vitro data from studies with human plasma indicate that amlodipine has no effect on protein binding of the drugs tested (digoxin, phenytoin, warfarin or indomethacin).

Simvastatin.

Co-administration of multiple doses of amlodipine and simvastatin resulted in an increase in exposure to simvastatin compared to simvastatin alone. The Product Information for simvastatin should be reviewed for the appropriate dose of simvastatin when the patient is prescribed amlodipine concurrently.

Grapefruit juice.

Grapefruit juice is known to inhibit the cytochrome P450 system, thereby affecting the pharmacokinetics of drugs such as calcium channel blockers. 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.

CYP3A4 inhibitors.

With concomitant use with the CYP3A4 inhibitor erythromycin in young patients and diltiazem in elderly patients, the plasma concentration of amlodipine was increased. The clinical relevance of this finding is uncertain. It cannot be ruled out that strong inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent than diltiazem. Amlodipine should be used with caution when administered with CYP3A4 inhibitors.

Clarithromycin.

Clarithromycin is an inhibitor of CYP3A4. There is an increased risk of hypotension in patients receiving clarithromycin with amlodipine. Close observation of patients is recommended when amlodipine is coadministered with clarithromycin.

CYP3A4 inducers.

There are no data available regarding the effect of CYP3A4 inducers on amlodipine. Concomitant use of CYP3A4 inducers (e.g. rifampicin, Hypericum perforatum (St John's Wort)) may decrease the plasma concentrations of amlodipine. Amlodipine should be used with caution when administered with CYP3A4 inducers.

Aluminium/ magnesium (antacid).

Coadministration of an aluminium/ magnesium antacid with a single dose of amlodipine had no significant effect on the pharmacokinetics of amlodipine.

Sildenafil.

A single 100 mg dose of sildenafil in 16 patients with essential hypertension had no effect on the pharmacokinetic parameters of amlodipine. When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.

Atorvastatin.

Coadministration of multiple 10 mg doses of amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady state pharmacokinetic parameters of atorvastatin.

Ethanol (alcohol).

Single and multiple 10 mg doses of amlodipine had no significant effect on the pharmacokinetics of ethanol.

Cyclosporin.

No drug interaction studies have been conducted with cyclosporin and amlodipine in healthy volunteers or other populations, with the exception of renal transplant patients. Various studies in renal transplant patients report that co-administration of amlodipine with cyclosporin affects the trough concentrations of cyclosporin, and consideration should be given for monitoring cyclosporin levels in renal transplant patients on amlodipine.

Tacrolimus.

There is a risk of increased tacrolimus blood levels when co-administered with amlodipine. 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.

Mechanistic target of rapamycin (mTOR) inhibitors.

mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a weak CYP3A inhibitor. Concomitant use of mTOR inhibitors and amlodipine may increase exposure of mTOR inhibitors.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In animal studies, amlodipine did not affect fertility in rats at oral doses up to 18 mg/kg (base) and had no teratogenic effects in rats (18 mg/kg) or rabbits (10 mg/kg).
(Category C)
Calcium channel blockers carry the potential to produce foetal hypoxia associated with maternal hypotension. Accordingly they should not be used in pregnant women unless the potential benefit outweighs the risk to the foetus.
The safety of amlodipine tablets in human pregnancy or lactation has not been established. Amlodipine (10 mg/kg as besilate salt, 7 mg/kg base), administered orally to rats at or near parturition induced a prolongation of gestation time, an increase in the number of stillbirths and a decreased postnatal survival.
 Experience in humans indicates that amlodipine is transferred into human breast milk. The median amlodipine concentration ratio of milk/plasma in 31 lactating women with pregnancy-induced hypertension was 0.85 following amlodipine administration at an initial dose of 5 mg once daily which was adjusted as needed (mean daily dose and body weight adjusted daily dose: 6 mg and 98.7 microgram/kg, respectively). The estimated daily dose of amlodipine in the infant via breast milk was 4.17 microgram/kg.
Breast-feeding should be discontinued during treatment with Amlodipine GH tablets.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Amlodipine tablets have been evaluated for safety in more than 11,000 patients in clinical trials worldwide. In general, treatment with amlodipine tablets was well tolerated at doses up to 10 mg daily. Most adverse events reported during therapy with amlodipine tablets were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine tablets (N = 1730) in doses up to 10 mg to placebo (N = 1250), discontinuation of amlodipine tablets due to adverse events was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). Amlodipine tablets therapy has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen or creatinine or liver function tests.
The most common side effects are headache and oedema. The incidence (%) of side effects which occurred in a dose related manner are as follows. (See Table 1.)
Other adverse experiences which were not clearly dose related but which were reported with an incidence greater than 1.0% in placebo controlled clinical trials include the following. (See Table 2.)
The following events occurred in ≤ 1% but > 0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship.

Blood and lymphatic system disorders.

Leucopenia, thrombocytopenia.

Cardiac disorders.

Tachycardia.

Ear and labyrinth disorders.

Tinnitus, vertigo.

Eye disorders.

Abnormal vision, conjunctivitis, diplopia, eye pain.

Gastrointestinal disorders.

Anorexia, constipation, dyspepsia*, dysphagia, diarrhoea, flatulence, vomiting, altered bowel habits, pancreatitis, gingival hyperplasia, dry mouth.

General disorders and administration site conditions.

Asthenia*, malaise, pain, rigors, thirst.

Immune system disorders.

Allergic reactions.

Investigations.

Weight gain.

Metabolism and nutrition disorders.

Anorexia, hyperglycaemia.

Musculoskeletal and connective tissue disorders.

Arthralgia, arthrosis, back pain, muscle cramps*, myalgia.

Nervous system disorders.

Hypoesthesia, paraesthesia, tremor, peripheral neuropathy, postural dizziness, syncope.

Psychiatric disorders.

Insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalisation, mood changes.

Renal and urinary disorders.

Micturition frequency, micturition disorder, nocturia.

Reproductive system and breast disorders.

Gynaecomastia, sexual dysfunction (male* and female).

Respiratory, thoracic and mediastinal disorders.

Dyspnoea*, epistaxis.

Skin and subcutaneous tissue disorders.

Alopecia, angioedema, pruritus*, purpura, rash*, rash erythematous, rash maculopapular, sweating increased.

Vascular disorders.

Hot flushes, hypotension, peripheral ischaemia, postural hypotension, vasculitis.
*These events occurred in less than 1% of patients in placebo-controlled trials, but the incidence of these adverse effects was between 1% and 2% in all multiple dose studies.
The following events occurred in ≤ 0.1% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discolouration, urticaria, skin dryness, dermatitis, erythema multiforme, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, xerophthalmia and weight decrease.
As with other calcium channel blockers the following adverse events have been rarely reported and cannot be distinguished from the natural history of the underlying disease: myocardial infarction, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) and chest pain.

Post-marketing experience.

There have been infrequent, postmarketing reports of hepatitis, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis). Some cases severe enough to require hospitalisation have been reported in association with use of amlodipine. In many instances, causal association is uncertain.
There have been post-marketing reports of extrapyramidal disorder in association with use of amlodipine.
Amlodipine tablets have been used safely in patients with chronic obstructive pulmonary disease, well compensated congestive heart failure, peripheral vascular disease, diabetes mellitus and abnormal lipid profiles.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Signs and symptoms.

Non-cardiogenic pulmonary oedema has rarely been reported as a consequence of amlodipine overdose that may manifest with a delayed onset (24-48 hours post-ingestion) and require ventilatory support. Early resuscitative measures (including fluid overload) to maintain perfusion and cardiac output may be precipitating factors.
Available data suggest that overdose might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. Dysrhythmias may occur following overdose with any calcium antagonists. Hypotension and bradycardia are usually seen within 1 to 5 hours following overdose. Hypotension can persist for longer than 24 hours despite treatment. Cardiac rhythm disturbances have been noted to persist for up to 7 days. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.
Reports of intentional overdose include a patient who ingested 250 mg and was asymptomatic and was not hospitalised; another patient (ingested 120 mg) was hospitalised, underwent gastric lavage and remained normotensive; a third patient (ingested 105 mg) was hospitalised and had hypotension (90/50 mmHg) which normalised following plasma expansion. Death resulted from a mixed overdose of amlodipine 140 mg and 10 mefenamic acid capsules in a 15 year old girl, and from a mixed overdose of amlodipine 70 mg and an unknown quantity of oxazepam in a 63 year old woman. A case of accidental drug overdose has been documented in a 19 month old male who ingested 30 mg amlodipine (about 2 mg/kg). During the emergency room presentation, vital signs were stable with no evidence of hypotension, but a heart rate of 180 bpm.

Recommended treatment.

If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine), should be considered with attention to circulating volume and urine output. Intravenous calcium may help to reverse the effects of calcium entry blockade.
Administration of activated charcoal to healthy volunteers immediately or up to 2 hours after ingestion of amlodipine 10 mg has been shown to significantly decrease amlodipine absorption. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected. Ipecac emesis is not recommended since haemodynamic instability and central nervous system (CNS) depression may rapidly develop. Since amlodipine is highly protein bound, dialysis is not likely to be of benefit.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Amlodipine is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth 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 characterised 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. The precise mechanism by which amlodipine relieves angina has not been fully determined but amlodipine reduces the total ischaemic burden by the following two actions.
1. 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.
2. Amlodipine has been shown to block constriction in main coronary arteries and coronary arterioles, induced by calcium, potassium, adrenaline, serotonin and thromboxane A2 analogue both in normal and in ischaemic regions.

Haemodynamics.

Following administration of therapeutic doses to patients with hypertension, amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing. Although the acute intravenous administration of amlodipine decreased arterial blood pressure and increased heart rate in haemodynamic studies of patients with chronic stable angina, chronic administration of oral amlodipine in clinical trials did not lead to clinically significant changes in heart rate or blood pressures in normotensive patients with angina.
With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients.
The magnitude of reduction in blood pressure with amlodipine is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105 to 114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90 to 104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressures (+1/-2 mmHg).
As with other calcium channel blockers, haemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine tablets have generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume. In haemodynamic studies, amlodipine tablets have not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and humans, even when coadministered with beta-blockers to humans. Similar findings, however, have been observed in normal or well compensated patients with heart failure with agents possessing significant negative inotropic effects.
In hypertensive patients with normal renal function, therapeutic doses of amlodipine tablets resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria.

Clinical trials.

Studies in patients with congestive heart failure.

Amlodipine tablets have been compared to placebo in four 8 to 12 week studies of patients with New York Heart Association (NYHA) class II/III heart failure, involving a total of 697 patients. Although efficacy in regard to the primary and secondary endpoints was not demonstrated, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or LVEF. In a long-term (follow-up at least 6 months, mean 13.8 months) placebo controlled mortality/ morbidity study of amlodipine tablets 5-10 mg in 1153 patients with NYHA classes III (N = 931) or IV (N = 222) heart failure on stable doses of diuretics, digoxin, and ACE inhibitors, amlodipine tablets had no effect on the primary endpoint of the study which was the combined endpoint of all cause mortality and cardiac morbidity (as defined by life threatening arrhythmia, acute myocardial infarction, or hospitalisation for worsened heart failure), or on NYHA classification, or symptoms of heart failure. Total combined all cause mortality and cardiac morbidity events were 222/571 (39%) for patients on amlodipine tablets and 246/583 (42%) for patients on placebo: the cardiac morbid events represented about 25% of the endpoints in the study.
In this study amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo.

Electrophysiologic effects.

Amlodipine does not change sinoatrial nodal function or atrioventricular conduction in intact animals or humans. In patients with chronic stable angina, intravenous administration of 10 mg of amlodipine and a further 10 mg of amlodipine after a 30 minute interval produced peripheral vasodilation and afterload reduction, but did not significantly alter A-H and H-V conduction and sinus node recovery time after pacing. Similar results were obtained in patients receiving amlodipine tablets and concomitant beta-blockers. In clinical studies in which amlodipine tablets were administered in combination with beta-blockers to patients with either hypertension or angina, no adverse events on electrocardiographic parameters were observed. In clinical trials with angina patients alone, amlodipine tablet therapy did not alter electrocardiographic intervals or produce higher degrees of AV blocks.

Effects in hypertension.

In patients with hypertension once daily dosing provides clinically significant reductions in blood pressure in both the supine and standing positions throughout the 24 hour interval postdose. Due to the slow onset of action, acute hypotension is not a feature of amlodipine administration. The blood pressure effect is maintained over the 24 hour dosing interval, with little difference in peak and trough effect. Tolerance has not been demonstrated in patients studied for up to 1 year. Effects on diastolic pressure were similar in young and older patients. The effect on systolic pressure was greater in older patients, perhaps because of greater baseline systolic pressure.

Effects in chronic stable angina.

In patients with angina, once daily administration of amlodipine increases total exercise time to angina onset and total work time to 1 mm ST segment depression and decreases both angina attack frequency and nitroglycerine tablet consumption. The sustained efficacy of amlodipine tablets in angina patients has been demonstrated over long-term dosing. In patients with angina there were no clinically significant reductions in blood pressures (4/1 mmHg) or changes in heart rate (+0.3 bpm).

Other.

In clinical trials amlodipine has shown no harmful effect on lipid levels. Dihydropyridine calcium channel blockers have not been associated with any adverse metabolic effects and are suitable for use in patients with asthma, diabetes and gout.

5.2 Pharmacokinetic Properties

Absorption.

After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6 and 12 hours postdose. This may reflect significant initial uptake by the liver, followed by a phase of redistribution. This interval is shorter (2 to 8 hours) in patients with hepatic insufficiency.

Distribution.

Absolute bioavailability has been estimated to be between 64% and 90%. The bioavailability of amlodipine is not altered by the presence of food. The volume of distribution is approximately 20 L/kg.
In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.

Metabolism/excretion.

The terminal plasma elimination half life is about 35 to 50 hours and is consistent with once daily dosing. Steady state plasma levels are reached after 7 to 8 days of consecutive dosing.
Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.

Special population.

Elderly (≥ 65 years).

In elderly hypertensive patients (mean age 69 years) there was a decrease in clearance of amlodipine from plasma as compared to young volunteers (mean age 36 years) with a resulting increase in the area under the curve (AUC) of about 60%.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

The carcinogenic potential of amlodipine has not been fully elucidated. Amlodipine did not induce any tumours when tested in rats at oral doses up to 2.5 mg/kg. This dose gave rise to plasma levels that are similar to those achieved clinically.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each Amlodipine GH tablet contains the following inactive ingredients: mannitol, microcrystalline cellulose, colloidal anhydrous silica, sodium starch glycollate, magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Amlodipine GH tablets should be stored below 30°C in the original packaging. Protect from light.

6.5 Nature and Contents of Container

Amlodipine GH tablets are supplied in PVC/PVDC/Aluminium foil blister packs in cartons of 30 tablets.

Australian registration numbers.

Amlodipine GH 5 mg tablets: AUST R 140104.
Amlodipine GH 10 mg tablets: AUST R 140140.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Amlodipine besilate is a dihydropyridine derivative. Amlodipine besilate is a white crystalline powder and is slightly soluble in water and sparingly soluble in ethanol.

Chemical structure.


Chemical Name: 3-ethyl 5-methyl-(4RS)-2-(2-(aminoethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate benzenesulphonate.
Molecular Formula: C20H25ClN2O5.C6H6O3S.
Molecular Weight: 567.1 (free base 408.9).

CAS number.

111470-99-6.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription only medicine.

Summary Table of Changes