VERAPAMIL TABLETS 40MG

Active substance: VERAPAMIL HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
VERAMIL
Verapamil Tablets 40 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Verapamil Hydrochloride BP 40 mg

3

PHARMACEUTICAL FORM
Film-coated tablet

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
1. The prophylaxis and treatment of angina pectoris.
2. Prophylaxis and treatment of supraventricular paroxysmal tachycardia;
atrial fibrillation and premature supraventricular contractions; atrial fibrillation
and flutter and supraventricular paroxysmal tachycardia of the reciprocating
type, associated with the Wolff-Parkinson-White Syndrome.
3. Treatment either alone or in conjunction with other anti-hypertensive
therapy of mild to moderate hypertension (including renal hypertension).

4.2

Posology and method of administration
Angina:
Adults:

120 mg t.d.s. is recommended. 80 mg t.d.s. can be completely
satisfactory in some patients with angina of effort. Less than 120

mg t.d.s. is not likely to be effective in angina at rest and variant
angina.
Children:

Not applicable.

Elderly:

As for adults, unless liver or renal function is impaired.

Supraventricular paroxysmal tachycardia:
Adults:
40-120 t.d.s. according to the severity of the condition.
Children:
Up to 2 years: 20 mg 2-3 t.d.s.
2 years and above: 40-120 mg 2-3 t.d.s. according to age and
effect.
Elderly:
It is recommended to commence with lowest dose and adjust as
required.
Hypertension:
Adults:
The usual dose range is 80-160 mg t.d.s. The dose should be
increased from 80 mg t.d.s. at weekly intervals according to
response, either alone or in conjunction with other
antihypertensive therapy. A further reduction in blood pressure
may be obtained by combining VERAMIL with other
antihypertensive agents, e.g. thiazide diuretics.
Children:

Up to 10 mg per kilo bodyweight per day in divided doses,
according to severity of disease.
Elderly:
It is recommended to commence with the lowest dose and adjust
as required.
Route of administration: Oral

4.3

Contraindications
Sick sinus syndrome, second or third degree atrioventricular block, cardiogenic
shock, acute myocardial infarction complicated by bradycardia, marked
hypotension or left ventricular failure, sino-atrial block, history of heart failure,
bradycardia of less than 50 beats/minute or hypotension of less than 90mmHg
systolic.
Atrial flutter or fibrillation complicating Wolff-Parkinson-White syndrome.
Porphyria.
Concomitant ingestion of grapefruit juice.

4.4

Special warnings and precautions for use
Care should be exercised when beta-blockers are administered either concurrently
or closely together because the effects of beta-blockers and VERAMIL may be

additive with respect to both contraction and conduction. This is particularly
important when either drug is administered intravenously.
VERAMIL should be used with caution in patients with first-degree
atrioventricular block because impulse conduction may be affected.
Left ventricular contractility may be affected by VERAMIL because of its mode
of action; cardiac failure may therefore be precipitated or, if it already exists, may
be aggravated by VERAMIL.
It is therefore important that VERAMIL should only be administered after
appropriate
therapy for cardiac failure has been instituted, e.g. digoxin etc. Patients with
impaired liver function exhibit reduced drug metabolism and therefore careful
attention should be paid to dosage in these patients.
The disposition of verapamil in patients with renal impairment has not been fully
established and therefore careful patient monitoring is recommended. Verapamil
is not
removed during dialysis.
VERAMIL should not be used in children with arrhythmias without specialist
advice; some supraventricular arrhythmias in childhood can be accelerated by
verapamil with dangerous consequences.
Patients starting therapy with simvastatin should be advised of the risk of
myopathy and told to report promptly unexplained muscle pain, tenderness or
weakness. A CPK level above 10x ULN in a patient with unexplained muscle
symptoms indicates myopathy. Simvastatin therapy should be discontinued if
myopathy is diagnosed or suspected. Periodic CPK determinations may be
considered (see section 4.5 ‘Interactions with other Medicaments and forms of
Interaction’).
Patients with rare hereditary problems of galactose intolerance, Lapp lactase
deficiency
or glucose/galactose malabsorbtion should not take Veramil.

4.5

Interaction with other medicinal products and other forms of interaction
VERAMIL increases the serum concentration of digoxin with increased risk AV
block and bradycardia; the awareness of the possibility of digitalis toxicity should
also be borne in mind.
Verapamil also increases the plasma concentration of imipramine and possibly
other
tricyclics, ciclosporin, theophylline and drugs under CYP-450 system (e.g.
buspirone,
dutasteride, eplerenone, atazanavir, ritonavir, sirolimus simvastatin).

There is an increased risk of myopathy when verapamil is given with simvastatin
(see
section 4.4 ‘Special Warnings and Precautions for Use’).
Verapamil inhibits the metabolism of midazolam; increased plasma-midazolam
increases
sedation.
The effects of carbamazepine and suxamethonium are enhanced by verapamil.
Verapamil enhances the effect of non-depolarising muscle relaxants (e.g.
atracurium,
pancuronium) possibly causing hypotension, myocardial depression and
hyperkalaemia.
Concomitant use of verapamil and intravenous dantrolene may cause hypotension,
myocardial depression and hyperkalaemia.
Grapefruit juice - an increase in verapamil serum level has been reported.
The effects of verapamil may be additive to other drugs which can produce a
hypotensive
effect. Examples of these are alcohol, aldesleukin, alprostadil, and anaesthetics
with risk of AV delay, antihypertensives, diuretics, antipsychotics, anxiolytics &
hypnotics, baclofen, isoflurane, levodopa, MAOIs, nitrates, nitroprusside and
tizanidine.
Hypotensive effect of calcium-channel blockers e.g. verapamil is antagonised
with
concomitant use of NSAIDs, corticosteroids or oestrogens.
Concomitant use of beta-blockers and verapamil may cause severe hypotension
and even
heart failure and should only be given together if myocardial function is well
preserved.
Enhanced hypotensive effect has been reported when calcium channel blockers
are given
with alpha-blockers. There is also an increased risk of first-dose hypotension with
postsynaptic alpha-blockers such as prazosin.
Cimetidine may inhibit metabolism of verapamil causing increased verapamilplasma
concentrations.
Amiodarone-induced risk of bradycardia, AV block and myocardial depression is
increased by verapamil.
There is possibly increased risk of bradycardia when calcium-channel blockers are
given with mefloquine.
Concomitant use of verapamil with disopyramide and flecainide increases risk of
myocardial depression and asystole.

Verapamil may raise the plasma concentration of quinidine resulting in extreme
hypotension.
Rifampicin increases the metabolism of verapamil thereby significantly reducing
its plasma concentration.
The effect of verapamil is also reduced by phenobarbitol, primidone and
phenytoin.
Neurotoxicity may occur without increased plasma-lithium concentrations in
patients given verapamil.

4.6

Pregnancy and lactation
Verapamil is not recommended for use during pregnancy unless the benefits of
the drug outweigh the possible hazards to the foetus.

4.7

Effects on ability to drive and use machines
Depending on individual susceptibility, the patient’s ability to drive a vehicle or
operate machinery may be impaired, particularly in the initial stages of treatment,
or when changing over from another drug. Verapamil has been shown to increase
the blood levels of alcohol and slow its elimination. Therefore, the effects of
alcohol may be exaggerated.

4.8

Undesirable effects
Administration of Verapamil is commonly associated with constipation.
Occasionally the following side-effects may be experienced: Nausea and
vomiting, flushing, headache, dizziness, fatigue ankle oedema, myalgia,
arthralgia, paraesthesia, and erythromelalgia; increased prolactin
concentration. On rare occasions gynaecomastia and gingival hyperplasia may
occur after long-term treatment, after intravenous administration of high doses,
hypotension, heart failure, bradycardia, heart block, and asystole.
Sensitivity or allergy to Verapamil is rare. Symptoms of allergy are erythema,
pruritis, urticaria, angioedema and Stevens-Johnson syndrome.

4.9

Overdose

The classical measures for cardiovascular side effects should be instituted
immediately. Cardiac arrest should be treated by heart massage, mechanical
respiration and the necessary intensive are appropriate to the condition should
be instituted.
In the case of hypotension, dopamine, noradrenalin or dobutamine may be
used together with appropriate positioning of the patient. Likewise, in
myocardial insufficiency treatment should be either dopamine, dobutamine,
cardiac glucosides or 10-20 ml of a 10% solution of calcium gluconate.
Second or third degree AV block should be treated with atropine or
isoprenaline and if necessary a pace maker should be used.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Verapamil is a Class 4 anti-arrhythmic agent which acts on supraventricular
arrhythmias through interfering with calcium conductants.

5.2

Pharmacokinetic properties
Verapamil is almost completely absorbed from the gastro-intestinal tract but is
subject to very considerable first-pass metabolism in the liver. The plasma
half-life is about 7 hours following oral administration and that of its active
metabolite which is norverapamil is about nine hours.
Verapamil acts within minutes of intravenous administration but its effects
may only last for about half-an-hour. It may require two hours to act after oral
administration with peak effect after five hours.
Verapamil is extensively bound to plasma proteins. The drug is mainly
excreted by the kidneys in the form of its metabolites, but some is also
excreted in the bile and in the faeces.

5.3

Preclinical safety data
Not applicable.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Malze Starch
Lactose
Gelatin
Colloidal Anhydrous Silica
Talc
Magnesium Stearate
Opaspray K-IF-3048
Hydroxypropylmethylcellulose 2190
Ethylcellulose
Diethylphthalate

6.2

Incompatibilities
None known.

6.3

Shelf life
24 months.

6.4

Special precautions for storage
Store below 25°C in a dry place in well closed containers.

6.5

Nature and contents of container
High density polystyrene with polythene lids and/or polypropylene containers
with polypropylene or polythene lids and polyurethane/polythene inserts.
Pack sizes: 100 and 500

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
11 Boumpoulinas Street,
3rd floor, 1060 Nicosia
Cyprus

8

MARKETING AUTHORISATION NUMBER(S)
PL 33414/0119

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
27/02/2009

10

DATE OF REVISION OF THE TEXT
27/02/2009

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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