Veramil 80 mg Film-coated Tablets

  • Name:

    Veramil 80 mg Film-coated Tablets

  • Company:
    info
  • Active Ingredients:

    verapamil hydrochloride

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 24/04/18

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Summary of Product Characteristics last updated on medicines.ie: 23/6/2019

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Orion Pharma (Ireland) Ltd

Orion Pharma (Ireland) Ltd

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Medicine Name Bufomix Easyhaler 80 micrograms/4.5 micrograms Active Ingredients Budesonide, Formoterol fumarate dihydrate
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Medicine Name Fareston Active Ingredients Toremifene Citrate
Medicine Name Indivina Active Ingredients Estradiol valerate, Medroxyprogesterone Acetate
Medicine Name Indivina 1 mg/2.5 mg tablets Active Ingredients Estradiol valerate, Medroxyprogesterone Acetate
Medicine Name Indivina 1 mg/5 mg tablets Active Ingredients Estradiol valerate, Medroxyprogesterone Acetate
Medicine Name Indivina 2 mg/5 mg tablets Active Ingredients Estradiol valerate, Medroxyprogesterone Acetate
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Medicine Name Methotrexate 2.5mg tablet Active Ingredients Methotrexate
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Medicine Name Stalevo 125 mg/31.25 mg/200 mg film-coated tablets Active Ingredients Carbidopa, Entacapone, Levodopa
Medicine Name Stalevo 150 mg/37.5 mg/200 mg film-coated tablets Active Ingredients Carbidopa, Entacapone, Levodopa
Medicine Name Stalevo 175 mg/43.75 mg/200 mg film-coated tablets Active Ingredients Carbidopa, Entacapone, Levodopa
Medicine Name Stalevo 200 mg/50 mg/200 mg film-coated tablets Active Ingredients Carbidopa, Entacapone, Levodopa
Medicine Name Stalevo 50 mg/12.5 mg/200 mg film-coated tablets Active Ingredients Carbidopa, Entacapone, Levodopa
Medicine Name Stalevo 75 mg/18.75 mg/200 mg film-coated tablets Active Ingredients Carbidopa, Entacapone, Levodopa
Medicine Name Toilax micro enema suspension Active Ingredients Bisacodyl
Medicine Name Veramil 120 mg Film-coated Tablets Active Ingredients verapamil hydrochloride
Medicine Name Veramil 40 mg Film-coated Tablets Active Ingredients verapamil hydrochloride
Medicine Name Veramil 80 mg Film-coated Tablets Active Ingredients verapamil hydrochloride
1 - 0 of 24 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 23 June 2019 SmPC

Reasons for updating

  • File format updated to PDF

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Updated SmPC format only.

Updated on 27 April 2018 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 24 April 2018 PIL

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 24 April 2018 PIL

Reasons for updating

  • Change to section 6 - date of revision

Updated on 24 May 2016 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 24 May 2016 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The following information has been added under 'Other Drug Interactions and Additional Drug Interaction Information ' (Section 4.5)

Dabigatran

When oral verapamil was co-administered with dabigatran etexilate (150 mg), a P- gp substrate, the Cmax and AUC of dabigatran were increased but magnitude of this change differs depending on time between administration and the formulation of verapamil. When verapamil 120 mg immediate -release was co- administered one hour before a single dose of dabigatran etexilate, the dabigatran Cmax was increased by about 180% and AUC by about 150%. No meaningful interaction was observed when verapamil was administered 2 hours after dabigatran etexilate (increase of Cmax by about 10% and AUC by about 20%).

Close clinical surveillance is recommended when verapamil is combined with dabigatran etexilate and particularly in the occurrence of bleeding, notably in patients having a mild to moderate renal impairment.

Updated on 19 May 2016 PIL

Reasons for updating

  • New PIL for new product

Updated on 4 January 2016 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The shelf life of the product has been reduced from five to three years.

Updated on 11 May 2015 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
  • Change due to harmonisation of SPC

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



Section 4.2 Posology and method of administration

·         The following information has been added: 

The dose of verapamil hydrochloride should be adjusted individually in accordance with the severity of disease. Long-standing clinical experience shows that the average daily dose in all indications is between 240 mg and 360 mg. The daily dose should not exceed 480 mg on a long-term basis, although a higher dose may be used for a short period. There is no limitation on the duration of use. Verapamil hydrochloride should not be discontinued abruptly after long-term use. It is recommended to taper the dosage.

Veramil Tablets should be used for patients likely to display a satisfactory response to low doses (e.g. patients with hepatic dysfunction of elderly patients). For patients requiring higher doses (e.g., 240 mg to 480 mg verapamil hydrochloride per day), formulations with a more suitable active drug content should be used.

Special Populations


Renal Impairment

Currently available data are described in Special Warnings and Precautions for Use section. Verapamil hydrochloride should be used cautiously and with close monitoring in patients with impaired renal function.


Liver Impairment

In patients with impaired liver function, metabolism of the drug is delayed to a greater or lesser extent depending on the severity of hepatic dysfunction, thus potentiating and prolonging the effects of verapamil hydrochloride. Therefore, the dosage needs to be adjusted with special cautions in patients with impaired liver function and low doses should be given initially (see Special Warnings and Precautions for Use section).

 

Section 4.3 Contraindications

·         The following information expands on and is in addition:

Atrial flutter or atrial fibrillation in the presence of an accessory bypass tract (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). These patients are at risk to develop ventricular tachyarrhythmia including ventricular fibrillation if verapamil hydrochloride is administered.

Heart failure with reduced ejection fraction of less than 35%, and/or pulmonary wedge pressure above 20 mm Hg (unless secondary to a supraventricular tachycardia amenable to verapamil therapy).

 

Section 4.4 Special warnings and precautions for use

·         The following information has been added:

Acute Myocardial Infarction
Use with caution in acute myocardial infarction complicated by bradycardia, marked hypotension, or left ventricular dysfunction.

Heart Block/1st Degree AV block/Bradycardia/Asystole
Verapamil hydrochloride affects the AV and SA nodes and prolongs AV conduction time. Use with caution as development of second-or third-degree AV block (contraindication) or unifascicular, bifascicular or trifascicular bundle branch block requires discontinuation reduction in subsequent doses or discontinuation of verapamil hydrochloride and institution of appropriate therapy, if needed.

Verapamil hydrochloride affects the AV and SA nodes and rarely may produce second-or third-degree AV block bradycardia, and, in extreme cases, asystole. This is more likely to occur in patients with a sick sinus syndrome (SA nodal disease), which is more common in older patients.

Asystole in patients other than those with sick sinus syndrome is usually of short duration (few seconds or less), with spontaneous return to AV nodal or normal sinus rhythm. If this does not occur promptly, appropriate treatment should be initiated immediately. See Undesirable Effects Section.

Digoxin
If verapamil is administered concomitantly with digoxin, reduce digoxin dosage. See Interactions with other medicinal drug products and other forms of interaction section.

Heart Failure
Heart failure patients with ejection fraction higher than 35% should be compensated before starting verapamil treatment and should be adequately treated throughout.

Hypotension
Intravenous verapamil hydrochloride often products a decrease in blood pressure below baseline levels that is usually transient and asymptomatic but may result in dizziness.

HMG-CoA Reductase Inhibitors (“Statins”) – See 4.5 Interaction with other medicinal products and other forms of interaction section

Section 4.5 Interaction with other medicinal products and other forms of interaction

·         The following information has been added:

In rare instances, including when patients with severe cardiomyopathy, congestive heart failure or recent myocardial infarction were given intravenous beta-adrenergic blocking agents or disopyramide concomitantly with intravenous verapamil hydrochloride, serious adverse effects have occurred.

Concomitant use of verapamil hydrochloride injection with agents that decrease adrenergic function may result in an exaggerated hypotensive response.

·         Potential Drug Interactions associated with Verapamil, the following information has been added:

Phenytoin:      
verapamil plasma concentrations
Colchicine:     
colchicine AUC (~2.0fold) and Cmax (~1.3fold), Reduce colchicine dose (see colchicine label)
Doxorubicin:   
doxorubicin AUC (104%) and Cmax (61%) with oral verapamil administration           
Digoxin:           Healthy subjects:
digoxin Cmax (~44%), digoxin C12h (~53%),  Css by ~45-53%42% and AUC (50%)
Cimetidine:     Cimetidine reduces verapamil clearance following intravenous verapamil administration
Everolimus:     everolimus:
AUC (~3.5fold) and Cmax (2.3fold), verapamil: Ctrough (~2.3fold), Concentration determinations and dose adjustments of everolimus may be necessary.
Sirolimus:        sirolimus levels:
AUC (~2.2fold), S-verapamil: AUC (~1.5fold), Concentration determinations and dose adjustments of sirolimus may be necessary.
Sulfinpyrazone:           No change in PK with intravenous verapamil administration

·         Other additional information:

Lithium:
Increased lithium neurotoxicity has been reported during concomitant verapamil hydrochloride-lithium therapy with either no change or an increase in serum lithium levels. The addition of verapamil hydrochloride, however, has also resulted in the lowering of the serum lithium levels in patients receiving chronic stable oral lithium. Patients receiving both drugs should be monitored carefully.

Neuromuscular blockers
Clinical data and animal studies suggest that verapamil hydrochloride may potentiate the effectactivity of neuromuscular blocking agents may be potentiated(curare-like and depolarizing). It may be necessary to decrease the dose of verapamil hydrochloride and/or the dose of the neuromuscular blocking agent when the drugs are used concomitantly.

Section 4.6 Fertility, pregnancy and lactation

·         The information has been expanded:

Pregnancy
Teratogenic Effects
There are no adequate and well-controlled study data in pregnant woman.

 

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

 

Because animal reproduction studies are not always predictive of human response during pregnancy (especially in the first trimester), Veramil Tabletsverapamil should only be used if considered essential by the physician.

 

Lactation
Verapamil is crosses the placental barrier and can be detected in umbilical vein blood at delivery.

 

Verapamil hydrochloride/metabolites are excreted in human breast milk. Verapamil concentrations in human milk

Limited data from oral administration has shown that the infant relative dose of verapamil is low (0.1-1% of the mothers oral dose) and that verapamil use may be variable but similar concentrations to those found in maternal plasma have been reportedcompatible with breastfeeding.

 

A risk to the newborns/infants cannot be excluded. Due to the potential for serious adverse reactions in nursing infants, verapamil should only be used during lactation if it is essential for the welfare of the mother.

 

4.7 Effects on ability to drive and use machines

·         This section has been reworded and expanded:

Due to its antihypertensive effect, depending on individual response, verapamil hydrochloride may affect the ability to react to the point of impairing the ability to drive a vehicle, operate machinery or work under hazardous conditions. This applies all the more at the start of treatment, when the dose is raised, when switching from another drug, and also in conjunction with alcohol.  Verapamil may increase the blood levels of alcohol and slow its elimination. Therefore, the effects of alcohol may be exaggerated.

 

4.8 Undesirable effects

·         This section has the following information added:

The most commonly reported ADRs were:

headache,

dizziness,

gastrointestinal disorders: nausea, constipation and abdominal pain,

bradycardia,

tachycardia,

palpitations,

hypotension,

flushing,

oedema peripheral,

fatigue.

 

Of unknown frequency:  paralysis (tetraparesis)1, Seizures, asystole, Muscular weakness, Myalgia, Arthralgia, Erectile dysfunction, Gynaecomastia, Galactorrhoea,

Rare:    Somnolence

1 There has been a single postmarketing report of paralysis (tetraparesis) associated with the combined use of verapamil and colchicine. This may have been caused by colchicine crossing the blood-brain barrier due to CYP3A4 and P-gp inhibitions by verapamil. See Interactions with other medicinal products and other forms of interaction section.

4.9  Overdose

·         The following information has been added:

Asystole should be handled by the usual measures including beta adrenergic stimulation (e.g. isoproterenol hydrochloride).

 

5.1 Pharmacodynamic properties

The following information has been added or updated:

Pharmacotherapeutic group: PhenylalkylamineSelective calcium channel blockers with direct cardiac effects, phenylalkylamine derivatives.


Verapamil hydrochloride is a white or practically white crystalline powder. It is practically odourless and has a bitter taste. It is soluble in water, freely soluble in chloroform, sparingly soluble in alcohol and practically insoluble in ether.

 

The chemical name of verapamil hydrochloride is benzeneacetonitrile, α-[3-[{2-(3, 4dimethoxyphenyl) ethyl} methylaminol] propyl]-3. 4-dimethoxy-α-(1-methylethyl) hydrochloride.

 

It has a molecular weight of 491.07 and the molecular formula is C27H38N204•HCl.

 

5.2 Pharmacokinetic properties

·         The following information has been added:

Verapamil hydrochloride is a racemic mixture consisting of equal portions of the R-enantiomer and the S-enantiomer. Verapamil is extensively metabolized. Norverapamil is one of 12 metabolites identified in urine, has 10 to 20% of the pharmacologic activity of verapamil and accounts for 6% of excreted drug. The steady-state plasma concentrations of norverapamil and verapamil are similar. Steady state after multiple once daily dosing is reached after three to four days.

 

Absorption

Greater than 90% of verapamil is rapidly absorbed from the small intestine after oral administration.  Mean systemic availability of the unchanged compound after a single dose of IR verapamil is 22% and that of SR verapamil approximately 33%, owing to an extensive hepatic first-pass metabolism. Bioavailability is about two times higher with repeated administration. Peak verapamil plasms levels are reached one to two hours after IR administration, and four to five hours after SR administration. The peak plasma concentration of norverapamil is attained approximately one and five hours after IR or SR administration, respectively. The presence of food has no effect on the bioavailability of verapamil.

 

Distribution

Verapamil is metabolised almost completely. The mainwidely distributed throughout the body tissues, the volume of distribution ranging from 1.8-6.8 L/kg in healthy subjects. Plasma protein binding verapamil is approximately 90%.

 

Metabolism

Verapamil is extensively metabolized. In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. In healthy men, orally administered verapamil hydrochloride undergoes extensive metabolism in the liver, with 12 metabolites are having been identified, most in only trace amounts. The major metabolites have been identified as various N and O-dealkylated products of verapamil. Of these metabolites, only norverapamil and the primary and secondary amines. In animal studies, only norverapamil showedhas any appreciable pharmacological activity, while the other metabolites were practically ineffective.effect (approximately 20% that of the parent compound), which was observed in a study with dogs

 

Elimination

Following intravenous infusion, verapamil is eliminated bi-exponentially, with a rapid early distribution phase (half-life about four minutes) and a slower terminal elimination phase (half-life two to five hours). Following oral administration, the elimination half-life is three to seven hours. Approximately 50% of an administered dose is eliminated renally within 24 hours, 70% within five days. Up to 16% of a dose is excreted in the feces. About 3% to 4% of renally excreted drug is excreted as unchanged drug. The total clearance of verapamil is nearly as high as the hepatic blood flow, approximately 1 L/h/kg (range: 0.7-1.3 L/h/kg).

 

Special Populations

Paediatric:

Limited information on the pharmacokinetics in the paediatric population is available. After intravenous dosing the mean half-life of verapamil was 9.17 hours and the mean clearance was 30L/h, whereas it is around 70 L/h for a 70kg adult. Steady-state plasma concentrations appear to be somewhat lower in the paediatric population after oral dosing compared to those observed in adults.

 

Geriatric: Aging may affect the pharmacokinetics of verapamil given to hypertensive patients. Elimination half-life may be prolonged in the elderly. The antihypersensitive effect of verapamil was found not to be age-related.

 

Renal insufficiency: Impaired renal function has no effect on verapamil pharmacokinetics, as shown by comparative studies in patients with end-stage renal failure and subjects with healthy kidneys. Verapamil and norverapamil are not significantly removed by haemodialysis.

 

Hepatic insufficiency: The half-life of verapamil is prolonged in patients with impaired liver function owing to lower oral clearance and a higher volume of distribution.

 

Verapamil hydrochloride, administered intravenously, has been shown to be rapidly metabolized.

 

5.3 Preclinical safety data

·         The following  information has been added:

Reproduction studies have been performed in rabbits and rats at oral verapamil doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are, however, no adequate and well-controlled studies in pregnant women.

Updated on 4 October 2012 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5 - Pharmacological properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The text has had a major review.  As a consequence there are changes to many sections in the SmPC.  In summary the changes are:

Section 4.2 - Verapamil should not be taken with grapefruit juice added to this section
Section 4.3 - Contraindications clarified
Section 4.4 - The following information has been added to special warnings and precautions for use:
  • Patients with heart failure or those who are susceptible to heart failure should be fully digitalised before verapamil therapy as it may aggravate or precipitate cardiac failure.
  • In patients with impaired hepatic function, the effect of verapamil is intensified and prolonged, depending
    on the severity of the liver disease, due to diminished drug metabolism. In these patients, dosage interval
    should be prolonged and low doses used.
  • Respiratory standstill has been reported for one patient with progressive muscular dystrophy following
    administration of Veramil Tablets.
  • Diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome,
    advanced Duchenne muscular dystrophy).
  • Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.
  • If acute cardiovascular side effects arise, treat as for overdose

Section 4.5 - the drug interactions table has been updated
Section 4.6 - During pregnancy (especially in the first trimester), Veramil Tablets should only be used if considered essential by the physician.
Section 4.7 - Warnings on ability to drive and use machines updated
Section 4.8 - Undesirable effects table updated
Section 4.9 - Overdose section updated
Section 5 - Pharmacological properties updated

Updated on 27 June 2011 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Date of text has been amended following product licence renewal

Updated on 9 December 2009 SmPC

Reasons for updating

  • Change to section 6.5 - Nature and contents of container

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change from a grey HDPE container to a white HDPE container
Removal of 30 pack size from SPC

Updated on 13 July 2009 SmPC

Reasons for updating

  • New individual SPC (was previously included in combined SPC)

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

None provided