SECURON IV

Patient Information Leaflet
(verapamil hydrochloride injection)

Securon IV


IMPORTANT INFORMATION
Read all of this leaflet carefully before you receive

Your doctor will monitor you closely if: ou have any other heart problems in addition to the Y one you are being treated for ou need any other medication to treat your abnormal Y heart rhythm You need to be given an anaesthetic You MUST tell your doctor if you are taking any medicines with or without a prescription or have recently taken any of the following medicines: eta-blockers used to treat high blood pressure and B heart conditions (these include atenolol, propranolol and metoprolol) lpha blockers used to treat high blood pressure and A heart conditions (these include prazosin and terazosin) edicines know as statins such as atorvastatin, M lovastatin, simvastatin used to lower cholesterol levels ny other medicine for high blood pressure or an A abnormal heart beat (arrhythmia) such as quinidine, flecainide, disopyramide, digoxin and digitoxin edicines used to treat depression (including the herbal M product St Johns Wort), anxiety or psychosis. These may include imipramine, buspirone and lithium edicines known as immunosuppressants such as M ciclosporin, sirolimus, everolimus and tacrolimus. These are used to prevent organ transplant rejection Glibenclamide, used to treat certain types of diabetes spirin , a non-steroidal anti-inflammatory painkiller A (NSAID) used to relieve pain and reduce fever Almotriptan, used to treat migraine Midazolam, used as a sedative or anaesthetic Theophylline used to treat asthma Cimetidine, used to treat indigestion or stomach ulcers ifampicin, used to treat tuberculosis and other types of R infection arbamazepine, phenytoin or phenobarbital (phenobarbitone). C These medicines are used as anti-convulsants Ritonavir, used to treat HIV rythromycin and telithromycin, used to treat types of E infection Colchicines or sulfinpyrazone, used to treat gout Driving and using machinery Verapamil may affect your ability to drive or operate machinery, you MUST check with your doctor before you do so.

Securon IV Keep this leaflet as you may need to read it again his leaflet provides a summary of the information T currently available on Securon IV or further information or advice ask your doctor or F ward pharmacist Tell your doctor if you experience any side effects

Leaflet contents: 1. 2. 3. 4. 5. 6. What is Securon IV and what is it used for? What should you know before receiving Securon IV? How will you receive Securon IV? Possible side effects How should Securon IV be stored? Further information about Securon IV

1. What is Securon IV and what is it used for? Securon IV belongs to a group of medicines called calcium channel blockers; its active ingredient is verapamil hydrochloride. Securon IV is used to treat abnormal heart rhythms such as an irregular or rapid heart rate. 2. What should you know before receiving Securon IV? I f the answer to any of the following questions is YES please tell your doctor or pharmacist BEFORE receiving Securon IV: re you are sensitive (allergic) to the active ingredient A verapamil hydrochloride or any of the other ingredients in the medicine? (See section 6) re you pregnant, planning to become pregnant or A breast-feeding? o you have kidney problems? D Do you have very low blood pressure? o you have an abnormally slow, fast or irregular D heartbeat? o you have or have you ever suffered from heart D problems such as heart failure, or the heart condition called Wolff-Parkinson-White syndrome? re you currently receiving intravenous beta-blockers, A e.g. atenolol, propranolol? o you have a condition where the nerve to muscle D transmission is affected e.g. myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy?

This is particularly important if you have had prolonged intravenous therapy or if you have switched to oral (tablet) treatment. Pregnancy and breast feeding lease discuss with your doctor if you are pregnant, P planning to become pregnant or are breast feeding. Other important information o NOT drink grapefruit juice whilst taking Securon IV as D it can effect the absorption of this medicine. This does not occur with other fruit juices such as orange, apple or tomato juice.

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FOR THE INFORMATION OF THE MEDICAL PROFESSION





1. 2. 3. 4.

(verapamil hydrochloride injection)
Trade Name of the Medicinal Product Securon IV Qualitative and Quantitative Composition Verapamil Hydrochloride BP 2.5 mg/ml Pharmaceutical Form Aqueous solution for intravenous injection. Clinical Particulars

Securon IV

I n vitro metabolic studies indicate that verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil has been shown to be an inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride while inducers of CYP3A4 have caused a lowering of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions. The following are potential drug interactions associated with verapamil: Acetylsalicylic acid C oncomitant use of verapamil with aspirin may increase the risk of bleeding

Alpha blockers Verapamil may increase the plasma concentrations of prazosin and terazosin which may have an additive hypotensive effect. Antiarrhythmics Verapamil may slightly decrease the plasma clearance of flecainide whereas flecainide has no effect on the verapamil plasma clearance. Verapamil may increase the plasma concentrations of quinidine. The combination of verapamil and antiarrhythmic agents may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure). Care must be exercised if Securon IV is combined with antiarrhythmic agents by any route. Anticonvulsants Verapamil may increase the plasma concentrations of carbamazepine. This may produce side effects such as diplopia, headache, ataxia or dizziness. Verapamil may also increase the plasma concentrations of phenytoin. Antidepressants Verapamil may increase the plasma concentrations of imipramine.

4.1. Therapeutic Indications Securon IV is indicated for the treatment of paroxysmal supraventricular tachycardia and the reduction of ventricular rate in atrial flutter/fibrillation. 4.2. Posology and Method of Administration For slow intravenous injection. Adults: 5-10 mg by slow intravenous injection over a period of 2 minutes. The patient should be observed continuously, preferably under ECG and blood pressure control. If necessary, e.g. in paroxysmal tachycardia, a further 5 mg may be given after 5 to 10 minutes. C hildren: Securon IV must always be administered under ECG monitoring i n young patients. 0 -1 year: 0.1-0.2 mg/kg bodyweight (usual single dose range: 0.75-2 mg). 1 -15 years: 0.1-0.3 mg/kg bodyweight (usual single dose range: 2-5 mg). The dose may be repeated after 30 minutes if necessary. Many cases are controlled by doses at the lower end of the range. The injection should be stopped at the onset of the desired effect. Elderly: The dosage should be administered over 3 minutes to minimise the risk of adverse effects. Dosage in impaired liver and renal function: Significant hepatic and renal impairment should not increase the effects of a single intravenous dose but may prolong its duration of action. F or use with beta-blocker therapy, see Contra-indications and Special Warnings and Precautions for Use. Hypersensitivity to the active substances or excipients. C ardiogenic shock; acute myocardial infarction complicated by bradycardia, marked hypotension or left ventricular failure; second or third degree AV block (except in patients with a functioning artificial ventricular pacemaker); sino-atrial block; sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker); uncompensated heart failure; bradycardia of less than 50 beats/minute; hypotension of less than 90 mmHg systolic; simultaneous administration of intravenous beta-blockers.

Antidiabetics Verapamil may increase the plasma concentrations of glibenclamide (glyburide). Anti-infectives Rifampicin may reduce the plasma concentrations of verapamil which may produce a reduced blood pressure lowering effect. Erythromycin, and telithromycin may increase the plasma concentrations of verapamil. Antineoplastics There is no significant difference between the pharmacokinetic parameters of doxorubicin with intravenous verapamil administration. Barbiturates Phenobarbital may reduce the plasma concentrations of verapamil.

4.3. Contra-indications

Benzodiazepines and other anxiolytics Verapamil may increase the plasma concentrations of buspirone and midazolam. Beta blockers Verapamil may increase the plasma concentrations of metoprolol and propranolol which may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure). Securon IV should not be given in combination with intravenous beta-blocker therapy and care must be exercised if Securon IV is combined with oral beta-blocker therapy. Cardiac glycosides Verapamil may increase the plasma concentrations of digitoxin and digoxin. Verapamil has been shown to increase the serum concentration of digoxin and caution should be exercised with regard to digitalis toxicity. The digitalis level should be determined and the glycoside dose reduced, if required. Colchicine Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (P-gp). Verapamil is known to inhibit CYP3A and P-gp. When verapamil and colchicine are administered together, inhibition of P-gp and/or CYP3A by verapamil may lead to increased exposure to colchicine. Combined use is not recommended. H2 Receptor antagonists Cimetidine may increase the plasma concentrations of verapamil following intravenous verapamil administration. HIV antiviral agents D ue to the metabolic inhibitory potential of some of the HIV antiviral agents, such as ritonavir, plasma concentrations of verapamil may increase. Caution should be used or dose of verapamil may be decreased.

Patients with atrial flutter/fibrillation in the presence of an accessory pathway (e.g. WPW syndrome) may develop increased conduction across the anomalous pathway and ventricular tachycardia may be precipitated. 4.4. Special Warnings and Precautions for Use V erapamil may affect impulse conduction. For this reason, Securon IV should be used with caution in patients with bradycardia or first degree AV block. Verapamil may affect left ventricular contractility; this effect is small and normally not important but cardiac failure may be precipitated or aggravated. In patients with poor ventricular function, therefore, Securon IV should only be given after cardiac failure has been controlled with appropriate therapy, e.g. digitalis. A lthough the pharmacokinetics of verapamil in patients with renal impairment are not affected, caution should be exercised and careful patient monitoring is recommended. Verapamil is not removed during dialysis. C aution should be exercised in treatment with HMG CoA reductase inhibitors (e.g., simvastatin, atorvastatin or lovastatin) for patients taking verapamil. These patients should be started at the lowest possible dose of verapamil and titrated upwards. If verapamil treatment is to be added to patients already taking an HMG CoA reductase inhibitor (e.g., simvastatin, atorvastatin or lovastatin), refer to advice in the respective statin product information.





Use with caution in the presence of diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy) 4.5. Interactions with other medicinal products and other forms of Interaction I n 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 with agents that decrease adrenergic function may result in an exaggerated hypotensive response.

Immunosuppressants Verapamil may increase the plasma concentrations of ciclosporin, everolimus, sirolimus and tacrolimus. Inhaled anaesthetics W hen used concomitantly, inhalation anaesthetics and calcium antagonists, such as verapamil hydrochloride, should each be titrated carefully to avoid additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).

Lipid lowering agents Verapamil may increase the plasma concentrations atorvastatin, lovastatin and simvastatin. MKP_78155604

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3. How will you receive Securon IV? ecuron IV is given to you by injection into a vein S (Intravenously). This will be carried out by a doctor. The dose will vary according to your condition this will be decided by the doctor. The medical team in the hospital may monitor your blood pressure and ECG (The electrical activity of the heart) throughout your treatment. The usual doses are as follows Adults: -10 mg by slow intravenous injection over a period 5 of 2 minutes. elderly patients, the injection may be given at a slower rate. In f necessary, an extra 5 mg may be injected after I 5 to 10 minutes. Children: 0-1 Year: 0.1 to 0.2 mg per kg bodyweight 1-15 years: 0.1 to 0.3 mg per kg bodyweight he injection may be repeated after 30 minutes, if T necessary. 4. Possible side effects s with all medicines, Securon IV can cause side A effects. Securon IV affects the rhythm of the heart, but may also slow down the heart rate and cause a drop in blood pressure in some patients. The medical team will therefore monitor you closely during your treatment. you experience any of the following rare side If effects tell your doctor IMMEDIATELY: hanges in heart rhythm, chest pains for the first time or C chest pains becoming frequent Swollen ankles nexpected wheezing, difficulty breathing, swelling of U the mouth, lips or tongue, itching or a severe skin rash Y ellowing of the skin or eyes, a fever or tenderness around the middle. These are signs that your liver may not be functioning as well as usual Other side effects with verapamil include flushing of the face or neck, sweating, headaches, tiredness, seizures, dizziness, vertigo, nervousness, movement disorders, abnormal discomfort, nausea, abdominal pain or vomiting. Other side effects may sometimes occur with long-term verapamil treatment. Tell your doctor if you develop swollen gums which spread over your teeth, or (in males) if your breasts swell. These effects are very rare and resolve on stopping treatment. f you experience any other unusual symptoms after I you have received Securon IV, tell your doctor, nurse or pharmacist 5. How should Securon IV be stored? Securon IV should be stored at a normal room temperature and protected from light, until it is given to you. The doctor or nurse will check that the expiry date on the label has not passed before you are given the injection. It should NOT be used after the expiry date printed on the label.

6. Further Information What Securon IV contains: ach ampoule of injection solution contains 2.5 mg E per ml verapamil hydrochloride ph Eur in water for injections and sodium chloride, with hydrochloric acid as pH adjuster What Securon IV looks like: he product is available in 2ml ampoules, each T containing 5mg of verapamil hydrochloride Marketing Authorisation and Manufacturer's Details Marketing Authorisation Holder: Abbott Laboratories Ltd., Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire. SL6 4XE. United Kingdom. Manufacturer: EBEWE Pharma GmbH Nfg.KG A-4866 Unterach, Austria. The leaflet was last approved

A Promise for Life

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Treatment with HMG CoA reductase inhibitors (e.g., simvastatin, atorvastatin or lovastatin) in a patient taking verapamil should be started at the lowest possible dose and titrated upwards. If verapamil treatment is to be added to patients already taking an HMG CoA reductase inhibitor (e.g., simvastatin, atorvastatin or lovastatin), consider a reduction in the statin dose and retitrate against serum cholesterol concentrations. A torvastatin may increase verapamil levels. Although there is no direct in vivo clinical evidence, there is strong potential for verapamil to significantly affect atorvastatin pharmacokinetics in a similar manner to simvastatin or lovastatin. Consider using caution when atorvastatin and verapamil are concomitantly administered. F luvastatin, pravastatin and rosuvastatin are not metabolized by CYP3A4 and are less likely to interact with verapamil.



S kin and subcutaneous tissue disorders: Steven-Johnson syndrome, erythema and hyperhidrosis.

Reproductive system and breast disorders: On very rare occasions, gynaecomastia has been observed in elderly male patients under long-term verapamil treatment; this was fully reversible in all cases when the drug was discontinued. Investigations: A reversible impairment of liver function characterized by an increase of transaminase and/or alkaline phosphatase may occur on very rare occasions during verapamil treatment and is most probably a hypersensitivity reaction. 4.9. Overdose T he symptoms of overdosage include hypotension, shock, loss of consciousness, first and second degree AV block (frequently as Wenckebachs phenomenon with or without escape rhythms), total AV block with total AV dissociation, escape rhythm, asystole, bradycardia up to high degree AV block and sinus arrest, hyperglycaemia, stupor and metabolic acidosis. Fatalities have occurred as a result of overdose. Treatment of overdosage depends on the type and severity of symptoms. The specific antidote is calcium, e.g. 10-20 ml of 10% calcium gluconate solution i.v. (2.25-4.5 mmol) if necessary by repeated injection or continuous infusion (e.g. 5 mmol/hour). The usual emergency measures for acute cardiovascular collapse should be applied and followed by intensive care. Verapamil hydrochloride cannot be removed by haemodialysis. Similarly, in the case of second or third degree AV block, atropine, orciprenaline, isoprenaline and if required, pacemaker therapy should be considered. If there are signs of myocardial insufficiency, dopamine, dobutamine, cardiac glycosides or calcium gluconate (10-20 ml of a 10% solution) can be administered. I n the case of hypotension, after appropriately positioning the patient, dopamine, dobutamine or noradrenaline may be given.



Lithium Serum levels of lithium may be reduced. However there may be increased sensitivity to lithium causing enhanced neurotoxicity. Neuromuscular blocking agents employed in anaesthesia The effects may be potentiated. Protein-bound drugs A s verapamil hydrochloride is highly bound to plasma proteins, it should be administered with caution to patients receiving other highly protein-bound drugs. Serotonin receptor agonists Verapamil may increase the plasma concentrations of almotriptan. Theophylline Verapamil may increase the plasma concentrations of theophylline.



Uricosurics Sulfinpyrazone may reduce the plasma concentrations of verapamil which may produce a reduced blood pressure lowering effect. Other Johns Wort may reduce the plasma concentrations of verapamil, whereas St. grapefruit juice may increase the plasma concentrations of verapamil. 4.6. Pregnancy and Lactation A lthough animal studies have not shown any teratogenic effects, verapamil should not be given during the first trimester of pregnancy unless, in the clinicians judgement, it is essential for the welfare of the patient. Verapamil is excreted into the breast milk in small amounts and is unlikely to be harmful. However, rare hypersensitivity reactions have been reported with verapamil. For this reason, it should only be used during lactation if, in the clinicians judgement, it is essential for the welfare of the patient. 4.7. Effects on Ability to Drive and Use Machines None stated. 4.8. Undesirable Effects A dverse events observed in clinical trials are depicted in the following table. Within each system organ class, the adverse drug reactions are ranked under headings of frequency, using the following convention: common (>1/100, <1/10), uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000), very rare (<1/10,000), including isolated reports.
System Organ Class Nervous system disorders common Cardiac disorders/vascular disorders - - - - - dizziness headache bradycardia hypotension tachycardia Frequency Undesirable Effects

Pharmacological Properties 5.1. Pharmacodynamic Properties Verapamil is a calcium antagonist which blocks the inward movement of calcium ions in cardiac muscle cells, in smooth muscle cells of the coronary and systemic arteries and in cells of the intracardiac conduction system. Because of its effect on the movement of calcium in the intracardiac conduction system, verapamil reduces automaticity, decreases conduction velocity and increases the refractory period. 5.2. Pharmacokinetic Properties F ollowing intravenous infusion in man, verapamil is eliminated bi-exponentially with a rapid distribution phase (half-life about 4 minutes) and a slower terminal elimination phase (half-life 2-5 hours). Plasma protein binding of verapamil is more than 90%. Renal insufficiency does not affect the kinetics of verapamil. In patients with liver cirrhosis, elimination half life is prolonged. 5.3. Preclinical Safety Data Not applicable. Pharmaceutical Particulars 6.1. List of Excipients W ater for injections, sodium chloride (8.5 mg/ml), hydrochloric acid as pH adjuster. 6.2. Incompatibilities Securon IV is incompatible with alkaline solutions. 6.3. Shelf Life 60 months. 6.4. Special Precautions for Storage Store at room temperature. Protect from light. 6.5. Nature and Contents of Container 2 ml glass ampoule (hydrolytic type 1) containing 5 mg verapamil. Pack size: 5 x 2 ml ampoules. 6.6. Instruction for Use/Handling None. Administrative Data 7. 8. 9. Marketing Authorisation Holder Abbott Laboratories Ltd., Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire. SL6 4XE. United Kingdom. Marketing Authorisation Number PL 00037/0367 Legal Category POM

common uncommon

Gastrointestinal disorders



uncommon

- -

nausea abdominal pain

C ases of seizures during verapamil hydrochloride injection have been reported. I n rare cases of hypersensitivity, bronchospasm accompanied by pruritis and urticaria has been reported.

Other Reactions from Postmarketing Surveillance or Phase IV Clinical Trials Other adverse events reported with verapamil are listed below by system organ class: Psychiatric disorders: on rare occasions, nervousness has been reported. Nervous system disorders: somnolence and extrapyramidal syndrome. Ear and labyrinth disorders: vertigo. Cardiac disorders/vascular disorders: decreased myocardial contractility has been reported. On rare occasions, 2nd and 3rd block may occur and in extreme cases, this may lead to asystole. The asystole is usually of short duration and cardiac action returns spontaneously after a few seconds, usually in the form of sinus rhythm. If necessary, the procedures for the treatment of overdosage should be followed as described below. On rare occasions, flushing has been reported. Gastrointestinal disorders: gingival hyperplasia may occur very rarely when the drug is administered over prolonged periods, and is fully reversible when the drug is discontinued. On rare occasions, vomiting has also been reported.

10. Date of First Authorisation/Renewal of Authorisation 17th June 2003 11. Date of (Partial) Revision of the Text TBA

A Promise for Life

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