Minitran 15

1. Name Of The Medicinal Product

Minitran 15

2. Qualitative And Quantitative Composition

Minitran 15 has a surface area of 20 sq cm and contains 54 mg of glyceryl trinitrate. The average amount delivered in 24 hours is 15 mg.

3. Pharmaceutical Form

Adhesive transdermal patch.

4. Clinical Particulars

4.1 Therapeutic Indications

Minitran 15 is indicated for:

Prophylaxis of angina pectoris either alone or in combination with other anti-anginal

therapy.

4.2 Posology And Method Of Administration

ADULTS:

1Prophylaxis of angina pectoris

The response to nitrates differs between individuals, and the minimum effective dose should be prescribed in each case. It is therefore recommended that treatment is started with one Minitran 5 patch per day, with upward dosage titration when necessary. Application can either be for a continuous period of 24 hours or intermittently, incorporating a patch free interval (usually at night). Attenuation of effect has occurred in some patients being treated with sustained release nitrate preparations. On the basis of current clinical studies it is recommended that in such cases Minitran should be applied daily with a patch free interval of 8 - 12 hours.

Each Minitran patch is contained in a sealed sachet. The adhesive layer is covered by a protective film, which should be removed before application. The Minitran patch should be applied to a clean, dry healthy area of skin on the torso or the arms.

Subsequent patches should not be applied to the same area of skin until several days have elapsed. The Minitran patch adheres easily to the skin, and also stays in place whilst bathing or during physical exercise.

4.3 Contraindications

Phosphodiesterase type 5 inhibitors such as Sildenafil. Tadalafil and Vardenafil have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contra-indicated. The use of glyceryl trinitrate is contra-indicated in cases of known hypersensivity to nitrates, severe anaemia, increased intra-ocular and intracranial pressure, and marked arterial hypotension. It is also contra-indicated in acute myocardial insufficiency due to obstruction as in aortic or mitral stenosis or of constrictive pericarditis.

4.4 Special Warnings And Precautions For Use

Minitran is not indicated for the treatment of acute angina attacks requiring rapid relief. Minitran should be used only under strict medical supervision in recent myocardial infarction or acute congestive cardiac insufficiency. Minitran should be used with caution in patients with hypoxaemia, severe anaemia or ventilation perfusion imbalance.

The appearance of cross-tolerance with other nitrates is possible.

The use of products for topical application, especially if prolonged, may give rise to sensitisation phenomena, in which case treatment should be suspended, and suitable therapeutic measures adopted.

Minitran does not contain any metal components, and therefore it is not considered necessary to remove the patch prior to diathermy or cardioversion.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiesterase type 5 inhibitors (eg. Sildenafil. Tadalafil. Vardenafil). Concomitant use of Minitran and other vasodilatory agents, calcium antagonists, beta-blockers, ACE inhibitors, neuroleptics, diuretics, antihypertensives, tricyclic antidepressants, and alcohol may decrease blood pressure. The effect of Minitran may be weakened by acetylsalicylic acid or other NSAID's. There is a risk of coronary artery constriction with concurrent administration of dihydroergotamine.

4.6 Pregnancy And Lactation

As with all drugs Minitran should not be prescribed during pregnancy, particularly during the first trimester, unless there are compelling reasons for doing so. It is not known whether the active substance passes into the breast milk. The benefits for the mother must be weighed against the risks for the child.

4.7 Effects On Ability To Drive And Use Machines

The product may give rise to postural hypotension, and it is therefore advisable to warn patients of this possibility, so that they avoid sudden positional changes at the start of treatment. Care should also be exercised when driving vehicles and operating machinery.

4.8 Undesirable Effects

Central Nervous System: Glyceryl trinitrate is generally well tolerated. The most frequently encountered side effect is headache, particularly when high doses are used; this usually disappears after a few days, but in particularly intense cases, it may be necessary to reduce the dose or interrupt treatment.

Cardio-vascular: Other undesirable effects observed, especially at the start of treatment, are: arterial hypotension (especially postural), tachycardia, fainting, palpitations, hot flushes, dizziness.

Gastro-intestinal: Nausea and vomiting are rarely observed.

Skin: Reddening of the skin, with or without itching or a slight erythematous reaction is occasionally observed. These effects, however, generally disappear a few hours after removal of the patch without adopting other measures. The site of application should be altered daily to avoid local irritation.

4.9 Overdose

High doses of glyceryl trinitrate may sometimes induce too rapid a reduction in arterial pressure, causing collapse. Due to the controlled release of glyceryl trinitrate from Minitran, overdosage is likely to be rare. In cases of suspected overdosage the Minitran patch should be removed and any reduction of the arterial blood pressure and symptoms of collapse should be treated by appropriate measures.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Nitroglycerin, the active constituent of Minitran is a dilator of smooth muscle, producing relaxation by an unknown mechanism. It has no direct effects on the inotropic or chronotropic state of the heart. It affects cardiac output only as a consequence of its effect on venous capacitance and arteriolar resistance vessels. These effects on preload and afterload reduce myocardial oxygen consumption and are primarily responsible for the mechanism by which nitroglycerin relieves the symptoms of angina pectoris. The drug's principal side effects (headache, flushing, dizziness, postural hypotension and tachycardia) are also a result of its smooth muscle relaxing effects.

5.2 Pharmacokinetic Properties

When Minitran is applied to the skin, nitroglycerin is absorbed continuously through the skin into the systemic circulation and thus reaches the target organs (heart, vascular system) before deactivation by the liver. Minitran gives continuous release of nitroglycerin over 24 hours maintaining constant plasma levels. Nitroglycerin is metabolised by hydrolysis to dinitrates and the mononitrate.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Isooctyl Acrylate/Acrylamide Copolymer (93:7)

Ethyl Oleate BP

Glyceryl Monolaurate

Low Density Polyethylene Film

One Side Silicone Coated Polyester Film

6.2 Incompatibilities

None known.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Minitran must be stored at room temperature (below 25°C) under exclusion of light and moisture.

6.5 Nature And Contents Of Container

Each patch is individually packed in a heat sealed foil sachet. Cartons contain 30 patches.

6.6 Special Precautions For Disposal And Other Handling

The patch is covered by a protective polyester film, which is detached and discarded before use.

7. Marketing Authorisation Holder

Meda Pharmaceuticals Ltd

249 West George Street

Glasgow

G2 4RB

Trading as:

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop's Stortford

CM22 6PU

8. Marketing Authorisation Number(S)

PL 15142/0087

9. Date Of First Authorisation/Renewal Of The Authorisation

28 February 1999/ 7 December 2005

10. Date Of Revision Of The Text

8^th December 2009