SEO PLR Content Directory Kiribati: Slozem 120mg, 180mg, 240mg, 300mg Capsules

1. Name Of The Medicinal Product

Slozem 120mg Capsules

Slozem 180mg Capsules

Slozem 240mg Capsules

Slozem 300mg Capsules

2. Qualitative And Quantitative Composition

Slozem 120mg Capsules each contain 120mg diltiazem hydrochloride

Slozem 180mg Capsules each contain 180mg diltiazem hydrochloride

Slozem 240mg Capsules each contain 240mg diltiazem hydrochloride

Slozem 300mg Capsules each contain 300mg diltiazem hydrochloride

For excipients, see 6.1.

3. Pharmaceutical Form

Prolonged release capsule, hard.

Slozem 120mg Capsules have a natural transparent cap with a pink transparent body and contain white-grey to light yellow approximately spherical pellets.

Slozem 180mg Capsules have a natural transparent cap with a pink opaque body and contain white-grey to light yellow approximately spherical pellets.

Slozem 240mg Capsules have a natural transparent cap with a scarlet opaque body and contain white-grey to light yellow approximately spherical pellets.

Slozem 300mg Capsules have an opaque white cap with an opaque scarlet body and contain white-grey to light yellow approximately spherical pellets.

4. Clinical Particulars

4.1 Therapeutic Indications

Mild to moderate hypertension. Angina pectoris.

4.2 Posology And Method Of Administration

Adults

240mg once daily

Dosage titration in 60mg to 120mg steps at 2-weekly intervals may be required to obtain satisfactory clinical response (usually 240mg to 360mg daily will suffice). Dosage should be reduced in the presence of adverse reactions or if the pulse rate falls below 50 per minute.

Elderly and patients with impaired hepatic or renal function

Starting dose 120mg once daily.

Children

Not recommended

4.3 Contraindications

In pregnancy and in women of childbearing potential. Slozem depresses atrioventricular node conduction and is therefore contraindicated in patients with marked bradycardia, sick sinus syndrome, uncontrolled heart failure or second or third degree AV block.

Hypersensitivity to diltiazem or any of the inactive ingredients.

As Slozem contains sucrose, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.4 Special Warnings And Precautions For Use

Slozem should be used with caution in patients with reduced left ventricular function. Patients with mild bradycardia, and/or having a prolonged PR interval, should be observed closely.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Drug combinations that may require dosage adjustment of diltiazem in the event of bradycardia

In common with other calcium antagonists, when Slozem is used with drugs which may induce bradycardia (e.g. amiodarone and beta-blockers) or with other antihypertensive drugs the possibility of an additive effect should be borne in mind.

Drug combinations that may require dosage adjustment of diltiazem in the event of increased hypotensive effects.

Concomitant use with alpha blockers such as prazosin should be strictly monitored because of the possible marked synergistic hypotensive effect of this combination.

Diltiazem has been used safely in combination with beta-blockers, diuretics, ACE inhibitors and other antihypertensive agents. It is recommended that patients receiving these combinations should be regularly monitored.

Cardiac Glycosides

Concomitant use of diltiazem and digoxin may cause small increases in plasma levels of digoxin.

H₂ receptor antagonists

In patients taking H₂ receptor antagonists concurrently with diltiazem, increased levels of diltiazem may be produced.

Anesthetics

Diltiazem hydrochloride treatment has been continued without problem during anaesthesia, but the anaesthetist should be informed that the patient is receiving a calcium antagonist.

CYP3A4 substrates

Oral administration of diltiazem can raise the blood levels of drugs exclusively metabolised by the iso-enzyme CYP3A4, leading to an increased the risk of adverse reactions (e.g., muscular disorders with statins):

• Increased plasma levels for carbamazepine, simvastatin, tacrolimus, sirolimus, and erythromycin.

• Increased total blood levels for ciclosporin

CYP1A2 substrates

Oral administration of diltiazem can also raise the plasma concentration of drugs exclusively metabolised by the isoenzyme CYP1A2 such as theophylline.

4.6 Pregnancy And Lactation

Diltiazem hydrochloride is teratogenic in some animal species. In the absence of adequate evidence of safety in human pregnancy Slozem should not be used in pregnancy or in women of child-bearing potential.

Nursing mothers:

Diltiazem hydrochloride is excreted in breast milk. One report suggests that concentrations in breast milk reach similar levels to those in serum. If use of Slozem is considered essential, an alternative method of infant feeding should be instituted.

4.7 Effects On Ability To Drive And Use Machines

None known

4.8 Undesirable Effects

The following have been reported: ankle oedema, malaise, headache, hot flushes, gastro-intestinal disturbances and very rarely symptomatic bradycardia, sino-atrial block and atrio-ventricular block.

Rashes and other cutaneous reactions have been reported in association with diltiazem. These reactions are generally mild and resolve on cessation of therapy; however, there have been occasional reports of severe vascular skin reactions, and of erythema multiforme. Acute generalised exanthematic pustulosis and hyperpigmentation in sun-exposed areas have also been reported.

Isolated cases of moderate and transient elevation of liver transaminases have been observed at the start of treatment. Isolated cases of clinical hepatitis have been reported which resolved on cessation of therapy.

The current literature suggests that the effects of vasodilation, particularly ankle oedema, are dose dependent and are more frequent in the elderly.

Gingival hyperplasia and drug-induced Parkinsonism may occasionally occur.

4.9 Overdose

Signs and symptoms:

Acute intoxication can lead to severe hypotension, bradycardia, first to third degree atrioventricular block and, on occasions, to cardiac arrest. Hyperglycaemia may require treatment. Onset of symptoms may be delayed for several hours after ingestion and have been described after as little as 900mg diltiazem.

Treatment:

Observation in a coronary or intensive care unit is advisable if a substantial overdose has been ingested. Soon after ingestion, gastric lavage followed by activated charcoal may reduce absorption. Profound hypotension requires plasma expanders, I V calcium gluconate and inotropic agents (e.g. dopamine, dobutamine or isoprenaline). Symptomatic bradycardia and heart block may respond to atropine, isoprenaline or, if necessary, cardiac pacing. Slozem capsules are extended release capsules and effects may be slow in onset and prolonged.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Diltiazem hydrochloride is a calcium antagonist. It selectively reduces calcium entry through voltage-dependent calcium channels into vascular smooth muscle cells and myocardial cells. This lowers the concentration of intracellular calcium which is available to active contractile proteins. In vascular tissue, diltiazem relaxes arterial smooth muscle, reducing systemic peripheral resistance and dilating the coronary arteries. In cardiac muscle diltiazem reduces contractility and slows the heart rate through its negative chronotropic and inotropic actions. Cardiac work and oxygen demand can therefore be reduced and high blood pressure lowered without reflex tachycardia.

5.2 Pharmacokinetic Properties

Diltiazem is well absorbed from the gastrointestinal tract and is subject to an extensive first-pass effect, giving an absolute bioavailability (compared to intravenous administration) of about 40%.

Diltiazem in plasma is 80-85% protein bound. Plasma levels above 40-50ng/ml are associated with pharmacological activity.

Diltiazem is extensively metabolised by the liver, the plasma elimination half-life being on average 3-4.5 hours.

The two major active circulating metabolites, desacetyl-diltiazem and N-monodesmethyl diltiazem possess coronary artery vasodilatory activity equivalent to about 50% of that of diltiazem. Only 0.2 to 4% diltiazem is found unchanged in the urine.

The prolonged release pellets in this presentation usually achieve maximum plasma diltiazem levels six to eight hours after dosing and have an apparent plasma half-life of approximately 7 hours, allowing once daily dosing

The bioavailability of diltiazem from the Slozem formulation given once a day is equivalent to that obtained from a conventional release tablet given three times a day, when the same total daily dose is administered.

Data from studies in patients and healthy volunteers have also demonstrated that trough plasma levels (i.e. 24 hours post dosing) can be maintained within the minimum therapeutic range by appropriate dose titration.

Plasma concentrations in elderly patients and in hepatic failure are in general higher than in young subjects, due to an increase in apparent bioavailability. In renal failure, a reduction in dosage is only necessary as a function of the clinical response

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Maize starch, sucrose, povidone, shellac, ethylcellulose, talc, gelatin, erythrosine (E127), indigo carmine (E132) and (180mg, 240mg and 300mg only), titanium dioxide (E171). Printing ink: black iron oxide (E172), shellac, propylene glycol.

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Slozem 120mg, 180mg and 240mg Capsules:

Do not store above 30°C.

Slozem 300mg Capsules:

Do not store above 25°C.

6.5 Nature And Contents Of Container

28 capsules in PVC/PVDC/Aluminium blisters enclosed in a cardboard carton.

6.6 Special Precautions For Disposal And Other Handling

None

7. Marketing Authorisation Holder

Merck Serono Ltd,

Bedfont Cross

Stanwell Road

Feltham

Middlesex

TW14 8NX

8. Marketing Authorisation Number(S)

Slozem 120mg Capsules PL 11648/0045

Slozem 180mg Capsules PL 11648/0046

Slozem 240mg Capsules PL 11648/0047

Slozem 300mg Capsules PL 11648/0042

9. Date Of First Authorisation/Renewal Of The Authorisation