Trangina XL

1. Name Of The Medicinal Product

TRANGINA XL 60mg TABLETS.

2. Qualitative And Quantitative Composition

Each tablet contains 60mg isosorbide-5-mononitrate.

3. Pharmaceutical Form

Prolonged-release tablets.

White, oval-shaped tablets impressed “C” on one face and the identifying letters “CY” on either side of a central division line on the reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

Prophylatic treatment of angina pectoris.

4.2 Posology And Method Of Administration

Posology

Adults: Isosorbide mononitrate (one tablet) once daily to be taken in the morning. The dose of 60mg may be increased to 120mg (two tablets) daily, both to be taken once daily in the morning. The dose can be titrated to minimise the possibility of headache, by initiating treatment with 30mg (half a tablet) for the first 2-4 days.

Isosorbide mononitrate tablets must not be chewed or crushed. They should be swallowed whole with half a glass of water.

Children: The safety and efficacy of isosorbide mononitrate in children has not been establised.

Elderly: No evidence of a need for routine dosage adjustment in the elderly has been found, but special care may be needed in those with increased susceptibility to hypotension or marked hepatic or renal insufficiency.

The core of the tablet is insoluble in the digestive juices but disintegrates into small particles when all active substance has been released. Very occasionally the matrix may pass through the gastrointestinal tract without disintegrating and be found visible in the stool, but all active substance has been released.

Method of Administration

For oral use.

4.3 Contraindications

Hypersensitivity to nitrates or any ingredients in the tablet.

Severe cerebrovascular insufficiency or hypotension are relative contraindications to the use of isosorbide mononitrate.

4.4 Special Warnings And Precautions For Use

Isosorbide mononitrate is not indicated for relief of acute angina attacks; in the event of an acute attack, sublingual or buccal glyceryl trinitrate tablets should be used.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Alcohol: enhanced hypotensive effect.

4.6 Pregnancy And Lactation

For isosorbide-5-mononitrate no clinical data on exposed pregnancies is available. Studies in animals have shown reproductive toxicity (see section 5.3). The relevance of these data for humans is unknown. Trangina XL 60mg Tablets should not be used during pregnancy unless clearly necessary.

4.7 Effects On Ability To Drive And Use Machines

Isosorbide-5-mononitrate has a moderate influence on the ability of an individual to drive and use machines. Isosorbide mononitrate may cause dizziness. Patients should make sure they are not affected before driving or operating machinery.

4.8 Undesirable Effects

Most of the adverse reactions are pharmacodynamic mediated and dose dependent. Headache may occur when treatment is initiated but usually disappears after continued treatment. Hypotension with symptoms such as dizziness and nausea has occasionally been reported. These symptoms generally disappear during long-term treatment.

4.9 Overdose

Symptoms: Pulsing headache. More serious symptoms are excitation, flushing, cold perspiration, nausea, vomiting, vertigo, syncope, tachycardia and a fall in blood pressure.

Treatment: Induction of emesis, activated charcoal. In case of pronounced hypotension the patient should first be placed in the supine position with legs raised. If necessary intravenous administration of fluid.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Isosorbide mononitrate is an active metabolite of the vasodilator isosorbide dinitrate.

Isosorbide-5-mononitrate is a potent venodilator and to a lesser extent an arterial dilator. Both intravenous and oral formulations reduce systemic arterial pressure and venous return, thereby lowering cardiac volume, dimensions and work. While the precise mechanism of action remains unclear, it is probably due to nitric oxide (NO) release which activates guanylate cyclase and increases the synthesis of cyclic GMP. It is possible that NO combines with sulphydryl groups in the endothelium and produces S-nitrosothiols that stimulate guanylate cyclase production. This is enhanced by N-acetylcysteine, which provides a source of sulphydryl groups. How cyclic GMP produces vascular relaxation is not exactly known.

5.2 Pharmacokinetic Properties

Isosorbide mononitrate is readily absorbed from the gastro-intestinal tract. Following oral administration of conventional tablets, peak plasma levels are reached in about 1 hour. Unlike isosorbide dinitrate, isosorbide mononitrate does not undergo first-pass hepatic metabolism and bioavailability is nearly 100%. Isosorbide mononitrate is widely distributed with a large apparent volume of distribution. It is taken up by smooth muscle cells of blood vessels and the nitrate group is cleaved to inorganic nitrite and then to nitric oxide. Isosorbide mononitrate is metabolised to inactive metabolites, including isosorbide and isosorbide glucuronide. Only 2% of isosorbide mononitrate is excreted unchanged in the urine. An elimination half-life of about 4 to 5 hours has been reported.

5.3 Preclinical Safety Data

High concentrations of isosorbide-5-mononitrate in rats are associated with prolonged gestation and parturition, stillbirths and neonatal death.

6. Pharmaceutical Particulars

6.1 List Of Excipients

The tablets also contain: lactose, hypromellose (E464), glyceryl palmitostearate, maize starch, magnesium stearate.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Shelf-life

Two years from date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

6.4 Special Precautions For Storage

Do not store above 25°C.

Keep container in the outer carton.

6.5 Nature And Contents Of Container

Aluminium (25µm)/PVC (250µm) strips in a carton box.

Pack sizes: 28, 56 (Al/PVC)

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Actavis UK Limited

(Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 0142/0462.

9. Date Of First Authorisation/Renewal Of The Authorisation

05 January 2001

Renewed – 12.03.2009

10. Date Of Revision Of The Text

12.03.2009