DUALPRESS FILM-COATED TABLET 5MG/10MG [SIN16490P]

Product Info

DUALPRESS FILM-COATED TABLET 5MG/10MG

[SIN16490P]

4.1. Therapeutic indications

The amlodipine/atorvastatin combination product (henceforth in this document termed “amlodipine/atorvastatin”) is indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate:

Amlodipine

Hypertension
The amlodipine component is indicated for the first line treatment of hypertension and can be used as the sole agent to control blood pressure (BP) in the majority of patients. Patients not adequately controlled on a single antihypertensive agent (other than amlodipine) may benefit from the addition of the amlodipine component of amlodipine/atorvastatin, in the same manner as they would benefit from the addition of amlodipine alone.

Coronary Artery Disease

Chronic Stable Angina
Amlodipine is indicated for the symptomatic treatment of chronic stable angina. Amlodipine may be used alone or in combination with other antianginal drugs.

Vasospastic Angina (Prinzmetal’s or Variant Angina)
Amlodipine is indicated for the treatment of confirmed or suspected vasospastic angina.

Amlodipine may be used as monotherapy, or in combination with other antianginal drugs.

Angiographically Documented Coronary Artery Disease
In patients with recently documented coronary artery disease (CAD) by angiography and without heart failure or an ejection fraction <40%, amlodipine is indicated to reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure.

Atorvastatin

Dyslipidemia
The atorvastatin component is indicated as an adjunct to diet for reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and triglycerides (TG) in patients with primary hypercholesterolemia, heterozygous familial hypercholesterolemia (FH) or combined (mixed) hyperlipidemia (Fredrickson Types IIa and IIb), elevated serum TG levels (Fredrickson Type IV), and in patients with dysbetalipoproteinemia (Fredrickson Type III) when response to diet and other non-pharmacological measures is inadequate.

The atorvastatin component also raises high-density lipoprotein cholesterol (HDL-C) and lowers the LDL-HDL and total-C/HDL ratios.

The atorvastatin component is also indicated as an adjunct to diet and other non-dietary measures in reducing elevated total-C, LDL-C and apo B in patients with homozygous FH.

Prevention of Cardiovascular Disease
Atorvastatin is indicated to reduce the risk of myocardial infarction (MI) in adult hypertensive patients without clinically evident coronary heart disease (CHD), but with at least three additional risk factors for CHD, such as age ≥55 years, male sex, smoking, left ventricular hypertrophy, other specified abnormalities on electrocardiogram (ECG), microalbuminuria or proteinuria, ratio of plasma total cholesterol to HDL-cholesterol ≥6, or premature family history of CHD.

In patients with Type 2 diabetes and without clinically evident CHD, but with multiple risk factors for CHD, such as retinopathy, albuminuria, smoking or hypertension, atorvastatin is indicated to:

• Reduce the risk of MI

• Reduce the risk of stroke

In patients with clinically evident CHD, atorvastatin is indicated to:

• Reduce the risk of non-fatal MI

• Reduce the risk of fatal and non-fatal stroke

• Reduce the risk for revascularization procedures

• Reduce the risk of hospitalization for congestive heart failure (CHF)

• Reduce the risk of angina

4.2. Posology and method of administration

General Considerations

The dosage range for amlodipine/atorvastatin is 5 mg/10 mg to a maximum dose of 10 mg/80 mg once daily. The starting dose and maintenance dose should be individualized on the basis of both effectiveness and tolerance for each individual component in the treatment of hypertension/angina and dyslipidemia. Current treatment guidelines should be consulted to establish treatment goals for patients based on their baseline characteristics. Doses may be taken at any time of day with or without food.

As a component of multiple-risk factor intervention, amlodipine/atorvastatin should be used in addition to non-pharmacological measures, including an appropriate diet, exercise and weight reduction in obese patients, smoking cessation, and to treat underlying medical problems, when the response to these measures have been inadequate.

Initial Therapy

Amlodipine/atorvastatin may be used to initiate treatment in patients with hyperlipidemia and either hypertension or angina. The recommended starting dose of amlodipine/atorvastatin should be based on the appropriate combination of recommendations for the amlodipine and atorvastatin components considered separately. The maximum dose of the amlodipine component of amlodipine/atorvastatin is 10 mg once daily. The maximum dose of the atorvastatin component of amlodipine/atorvastatin is 80 mg once daily.

Substitution Therapy

Amlodipine/atorvastatin may be substituted for its individually titrated components. Patients may be given the equivalent dose of amlodipine/atorvastatin or a dose of amlodipine/atorvastatin with increased amounts of amlodipine, atorvastatin or both for additional antianginal effects, BP lowering, or lipid-lowering effect.

Amlodipine/atorvastatin may be used to provide additional therapy for patients already on one of its components. As initial therapy for one indication and continuation of treatment of the other, the recommended starting dose of amlodipine/atorvastatin should be selected based on continuation of the component being used previously and on the recommended starting dose for the component being added.

Concomitant Medication (see also section 4.5. Interaction with other medicinal products and other forms of interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

The amlodipine component of amlodipine/atorvastatin has been safely co-administered with thiazide diuretics, alpha blockers, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, long-acting nitrates, and with sublingual nitroglycerine. Amlodipine/atorvastatin has also been safely administered with the aforementioned medicines.

The atorvastatin component of amlodipine/atorvastatin may be used in combination with a bile acid-binding resin for additive effect on lipid lowering. The combination of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and fibrates should generally be avoided (see sections 4.4. Special warnings and precautions for use and 4.5. Interaction with other medicinal products and other forms of interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Amlodipine (Hypertension or Angina)

For both hypertension and angina, the usual initial dose is 5 mg amlodipine once daily which may be increased to a maximum of 10 mg depending on the individual patient’s response.

In general, titration should proceed over 7–14 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.

Coronary Artery Disease (Amlodipine Studies)

For patients with CAD the recommended dosage range is 5 mg to 10 mg of amlodipine once daily. In clinical studies, the majority of patients required 10 mg once daily (see section 5.1. Pharmacodynamic properties – Amlodipine/Atorvastatin Pharmacodynamics – Use in Patients with CAD – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Atorvastatin (Hyperlipidemia)

The patient should be placed on a standard cholesterol-lowering diet before receiving atorvastatin and should continue on this diet during treatment with atorvastatin. The recommended starting dose of atorvastatin is 10 mg or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range is 10 mg to 80 mg once daily. After initiation and/or upon titration of atorvastatin, lipid levels should be analysed within 2 to 4 weeks, and dosage adjusted accordingly.

Prevention of Cardiovascular Disease

For primary prevention, the recommended dose is 10 mg once daily. For secondary prevention, optimal dosing may range from 10 mg to 80 mg atorvastatin once daily, to be given at the discretion of the prescriber, taking into account the expected benefit and safety considerations relevant to the patient to be treated (see section 5.1. Pharmacodynamic properties – Secondary Prevention of Cardiovascular Events – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Primary Hypercholesterolemia and Combined (Mixed) Hyperlipidemia (Atorvastatin Studies)

The majority of patients are controlled with 10 mg of atorvastatin once daily. A therapeutic response is evident within 2 weeks, and the maximum response is usually achieved within 4 weeks. The response is maintained during chronic therapy.

Homozygous Familial Hypercholesterolemia (Atorvastatin Studies)

In a compassionate-use study of patients with homozygous FH, most patients responded to 80 mg of atorvastatin with a greater than 15% reduction in LDL-C (18%–45%).

Use in Patients with Impaired Hepatic Function

Amlodipine/atorvastatin should not be used in patients with hepatic impairment (see sections 4.3. Contraindications and 4.4. Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Use in Patients with Impaired Renal Function

No adjustment of the dose is required in patients with impaired renal function (see section 4.4. Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Use in the Elderly

No adjustment of the dose is required in elderly patients.

Use in Children

Safety and effectiveness in children have not been established for amlodipine/atorvastatin.

Use in Combination with Other Medicinal Compounds

In cases where co-administration of atorvastatin with cyclosporine, telaprevir, or the combination tipranavir/ritonavir is necessary, the dose of atorvastatin should not exceed 10 mg.

Dose of atorvastatin should not exceed 20 mg/day with concomitant use with elbasvir/grazoprevir (see sections 4.4. Special warnings and precautions for use – Skeletal Muscle Effects and 4.5. Interaction with other medicinal products and other forms of interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Use of atorvastatin is not recommended in patients taking letermovir co-administered with cyclosporine.

Pharmacokinetic drug interactions that result in increased systemic concentration of atorvastatin have also been noted with other human immunodeficiency virus (HIV) protease inhibitors (lopinavir/ritonavir, saquinavir/ritonavir, darunavir/ritonavir, fosamprenavir, fosamprenavir/ritonavir and nelfinavir), hepatitis C (HCV) protease inhibitors (boceprevir, elbasvir/grazoprevir, simeprevir), clarithromycin, itraconazole and letermovir. Caution should be used when co-prescribing atorvastatin and appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin is employed (see sections 4.4. Special warnings and precautions for use – Skeletal Muscle Effects and 4.5. Interaction with other medicinal products and other forms of interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3. Contraindications

Amlodipine/atorvastatin is contraindicated in patients who:

1. Have known hypersensitivity to dihydropyridines*, amlodipine, atorvastatin, or any component of this medication.

2. Have active liver disease or unexplained persistent elevations of serum transaminases >3 x the upper limit of normal [ULN].

3. Are pregnant, breast-feeding, or of childbearing potential who are not using adequate contraceptive measures. Amlodipine/atorvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards to the fetus.

4. Are concomitantly treated with glecaprevir/pibrentasvir.

*Amlodipine is a dihydropyridine calcium channel blocker.