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. Prophy laxis and treatment of suprav entricular paroxy smal tachycardia; atr ial
fibrillation and premature supraventricular contractions; atrial fibrillation and fl utter
and s upraventricular pa roxysmal t achycardia of t he re ciprocating ty pe, a ssociated
with the Wolff-Parkinson-White Syndrome.
3. Tre atment ei ther alone or in conjunction with other ant i-hypertensive the rapy 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, sec ond or t hird deg ree at rioventricular 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 pa rticularly 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 affec ted by V ERAMIL because of its mode of
action; c ardiac fa ilure m ay the refore be pr ecipitated or, if it a lready exi sts, m ay be
aggravated by VERAMIL.
It is the refore important tha t VERAMIL should only be adm inistered 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 an d t herefore careful pa tient m onitoring i s re commended. Verapamil i s
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 a dvised of th e risk of m yopathy
and told to report promptly unexplained muscle pain, tenderness or weakness. A CPK
level ab ove 10x ULN in a pat ient wi th un explained m uscle sy mptoms indicate s
myopathy. Si mvastatin therapy should be di scontinued if m yopathy is diag nosed or
suspected. Pe riodic CPK dete rminations m ay be cons idered (see s ection 4. 5
‘Interactions with other Medicaments and forms of Interaction’).
Patients w ith rare her editary prob lems of g alactose in tolerance, L app lac tase
deficiency
or glucose/galactose malabsorbtion should not take Veramil.

4.5

Interaction with other medicinal products and other forms of interaction
VERAMIL incre ases th e serum concen tration o f d igoxin with increased risk AV
block and br adycardia; t he aw areness o f the possibility of dig italis tox icity sh ould
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 in hibits the m etabolism of
increases

midazolam; incre ased p lasma-midazolam

sedation.
The effects of carbamazepine and suxamethonium are enhanced by verapamil.
Verapamil enhances the effect of non-depolarising muscle relaxants (e.g. atracurium,
pancuronium) possib ly causi ng hy potension,
hyperkalaemia.

myocardial d epression and

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 e ffects o f v erapamil m ay be addi tive to other d rugs whi ch c an produce a
hypotensive
effect. Examples of t hese are alcohol, aldesleukin, alprostadil, and anaesthetics with
risk of AV del ay, anti hypertensives, diu retics, ant ipsychotics, anxio lytics &
hypnotics, bac lofen, isoflurane, lev odopa, MAOIs, nit rates, n itroprusside an d
tizanidine.
Hypotensive effect of calcium-channel blockers e.g. verapamil is antagonised with
concomitant use of NSAIDs, corticosteroids or oestrogens.
Concomitant use of be ta-blockers and v erapamil may cause s evere hypotension and
even
heart fa ilure and sho uld only be g iven tog ether if myocardial fun ction i s wel l
preserved.
Enhanced hy potensive effe ct has be en rep orted when calc ium channel bl ockers ar e
given
with al pha-blockers. There is also an increased ri sk of fi rst-dose hy potension with
postsynaptic alpha-blockers such as prazosin.
Cimetidine may inhibit metabolism of verapamil causing increased verapamil-plasma
concentrations.
Amiodarone-induced r isk of brady cardia, AV blo ck and m yocardial depr ession is
increased by verapamil.

There i s poss ibly increa sed risk of brady cardia w hen calc ium-channel bl ockers ar e
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 fo llowing side- effects may be experi enced: N ausea a nd v omiting, flus hing,
headache, d izziness, fatigue ank le oe dema, m yalgia, ar thralgia, p araesthesia, an d
erythromelalgia; increased prolactin concentration. On rare occasions gynaecomastia
and g ingival hy perplasia may occur aft er lo ng-term trea tment, aft er i ntravenous
administration of high doses, hypotension, heart failure, bradycardia, heart block, and
asystole.
Sensitivity o r all ergy t o Verapamil i s ra re. S ymptoms o f a llergy a re er ythema,
pruritis, urticaria, angioedema and Stevens-Johnson syndrome.

4.9

Overdose
The c lassical m easures for cardiovascular s ide effects sh ould be instituted
immediately. C ardiac arrest sh ould be treated b y heart m assage, m echanical
respiration a nd th e ne cessary int ensive are appropriate to the c ondition sh ould be
instituted.
In the ca se o f hypotension, dop amine, no radrenalin or dobu tamine m ay be used
together wi th appropriate posi tioning of the p atient. L ikewise, in m yocardial
insufficiency treatment should be either dopamine, dobutamine, cardiac glucosides or
10-20 ml of a 10% solu tion of calcium gluconate. Second or t hird degree AV block
should be treated with atropine or isoprenaline and if necessary a pace m aker 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
Maize 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 deg C in a dry place in well closed containers.

6.5

Nature and contents of container
High density poly styrene with po lythene l ids an d/or poly propylene con tainers 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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