ViATIM

1. Name Of The Medicinal Product

ViATIM, Suspension and solution for injection in a pre-filled dual chamber syringe.

Hepatitis A (inactivated, adsorbed) and Typhoid polysaccharide vaccine

2. Qualitative And Quantitative Composition

The dual chamber syringe contains 0.5 millilitre of purified Vi polysaccharide typhoid vaccine and 0.5 millilitre of inactivated hepatitis A vaccine which are mixed prior to administration.

After reconstitution, 1 dose (1ml) contains:

Originally contained in the suspension:

Hepatitis A virus, GBM strain (inactivated)^1,2………….160 U³

¹ produced in human diploid (MRC-5) cells

² adsorbed on aluminium hydroxide, hydrated (0.3 milligrams Al)

³ In the absence of an international standardised reference, the antigen content is expressed using an in-house reference

Originally contained in the solution:

Salmonella typhi (Ty 2 strain) capsular Vi polysaccharide………25 micrograms

Excipient(s):

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Suspension and solution for suspension for injection in a pre-filled dual chamber syringe.

The vaccine is presented in a dual-chamber syringe.

The purified Vi polysaccharide typhoid vaccine (solution for injection) is contained in the chamber of the syringe closest to the needle, and the inactivated hepatitis A vaccine (suspension for injection) in the chamber closest to the plunger.

The component Hepatitis A (inactivated, adsorbed) is a cloudy and white suspension and the component Typhoid polysaccharide is a clear and colourless solution.

4. Clinical Particulars

4.1 Therapeutic Indications

ViATIM is indicated for simultaneous active immunisation against typhoid fever and hepatitis A virus infection in subjects from 16 years of age.

ViATIM should be given in accordance with official recommendations.

4.2 Posology And Method Of Administration

Posology

The recommended dosage for subjects of at least 16 years of age is 1 millilitre of the mixed vaccine.

Initial protection is achieved with one single dose of ViATIM. Protective levels of antibody may not be reached until 14 days after administration of the vaccine.

In order to provide long-term protection against infection caused by the hepatitis A virus, a second dose (booster) of an inactivated hepatitis A vaccine should be given. ViATIM may be be used to provide one or both doses of hepatitis A vaccine as follows:

• In subjects who have received one dose of ViATIM:

- either a dose of monovalent hepatitis A vaccine should be given within 36 months and preferably within 6 to 12 months (see section 5.1)

- or, if continued protection against typhoid is also required, a second dose of ViATIM may be given provided that approximately 36 months have elapsed since the first dose.

• In subjects who have received one dose of monovalent hepatitis A vaccine:

- ViATIM may be used to provide the second dose (booster) of hepatitis A vaccine if protection against typhoid fever is also desirable. It should be given within 36 months of the hepatitis A vaccine and preferably within 6 to 12 months.

It is predicted that HAV antibodies persist for many years (beyond 10 years) after the second dose (booster).

In subjects who remain at risk of typhoid fever, revaccination against typhoid fever should be carried out with a single dose of a purified Vi polysaccharide typhoid vaccine every 3 years, (see section 5.1).

Method of administration

ViATIM should be administered by slow intramuscular injection in the deltoid region.

ViATIM must not be administered intravascularly.

ViATIM should not be administered into the buttocks due to the varying amount of fatty tissue in this region, nor by the intradermal route, since these methods of administration may induce a weaker immune response. ViATIM may be administered by the subcutaneous route in patients with thrombocytopenia or in those at risk of haemorrhage.

See section 6.6 for instructions for preparation.

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients or to neomycin (present in trace amounts as a residual of the manufacturing process).

Vaccination should be delayed in subjects with an acute severe febrile illness.

4.4 Special Warnings And Precautions For Use

As with all vaccines, appropriate facilities and medication such as epinephrine (adrenaline) should be readily available for immediate use in case of anaphylaxis or hypersensitivity following injection.

Immunogenicity of ViATIM could be impaired by immunosuppressive treatment or in immunodeficient subjects. It is recommended to delay vaccination until the completion of any immunosuppressive treatment. Subjects with chronic immunodeficiency such as HIV infection may be vaccinated if the underlying immunodeficiency allows the induction of an antibody response, even if limited.

Because of the incubation period of hepatitis A disease, infection may be present but not clinically apparent at the time of vaccination. It is not known whether ViATIM will prevent hepatitis A in this case.

ViATIM does not protect against infection caused by other known liver pathogens including hepatitis B, hepatitis C and hepatitis E viruses.

ViATIM does not protect against infection by Salmonella enterica other than serotype typhi.

As with any vaccine, a protective immune response may not be elicited in all vaccinees.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

ViATIM must not be mixed with any other vaccine in the same syringe.

ViATIM is a combination of purified Vi polysaccharide typhoid vaccine and inactivated hepatitis A vaccine. Although concomitant administration with other inactivated vaccines using different syringes and at different injection sites has not been specifically studied, it is anticipated that no interaction will be observed.

Concomitant administration of yellow fever vaccine with ViATIM has not been specifically assessed. However, based on data obtained from the concomitant administration of the monovalent vaccines (purified Vi polysaccharide typhoid vaccine and inactivated hepatitis A vaccine) with yellow fever vaccine, no interference with the immune responses to any of these antigens would be expected.

The effect of concomitant administration of immunoglobulins on the immunogenicity of ViATIM has not been assessed. Therefore, interference with the immune response of ViATIM cannot be ruled out. Data obtained from concomitant administration of immunoglobulins with the monovalent inactivated hepatitis A vaccine showed that anti-HAV seroconversion rates were not modified whereas anti-HAV antibody titres could be lower than after vaccination with the monovalent vaccine alone.

4.6 Pregnancy And Lactation

Pregnancy

Data on a limited number (more than 150 cases with monovalent Vi polysaccharide typhoid vaccine, more than 40 cases with monovalent inactivated hepatitis A vaccine and more than 10 cases with ViATIM or the two components given simulatenously) of exposed pregnancies indicate no adverse effects of ViATIM on pregnancy or on the health of the foetus/new born child. To date no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or post-natal development (see section 5.3).

Caution should be exercised when prescribing to pregnant women.

When the patient is considered to be at risk of only one of hepatitis A or typhoid fever, the monovalent vaccine should be used.

Lactation

It is unknown whether ViATIM is excreted in human breast milk. The excretion of ViATIM in milk has not been studied in animals. A decision on whether to continue/discontinue breast-feeding or to administer or not administer ViATIM should be made taking into account the benefit of breast-feeding to the child and the benefit of ViATIM to the woman.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed. Dizziness has been observed as an uncommon reaction (>1/1000, <1/100) following administration of this vaccine (see section 4.8).

4.8 Undesirable Effects

Adverse event data are derived from clinical trials and worldwide post marketing experience.

Within each system organ class the adverse events are ranked under headings of frequency, most frequent reactions first, using the following convention:

Very common (>1/10), Common (>1/100, <1/10), Uncommon (>1/1000, <1/100), Rare (>1/10000, <1/1000), Very rare (<1/10000), including isolated reports.

Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.

Clinical Studies

The safety profile of ViATIM was evaluated in nearly 1100 subjects included in 5 clinical studies. The most commonly reported reactions were those occurring at the injection site.

The adverse reactions observed with ViATIM were as follows:

Nervous system disorders

Very common: headache.

Uncommon: dizziness.

Gastrointestinal disorders

Common: nausea, diarrhoea.

Skin and subcutaneous tissue disorders

Uncommon: pruritus, rash.

Musculoskeletal and connective tissue disorders

Very common: myalgia.

Common: arthralgia.

General disorders and administration site conditions

Very common: malaise, asthenia, injection site disorders (pain, induration, oedema, erythema).

Common: fever.

Pain at the ViATIM injection site was reported in 89.9% of subjects (severe in 4.5%). For subjects who received the two monovalent vaccines concomitantly at separate injection sites, pain was reported in 83.2% of subjects (severe in 5.0%) for both vaccine sites combined. Pain was reported by 79.3% of subjects (severe in 5.0%) at the Vi vaccine site and by 50.3% of subjects (severe in 0.6%) at the hepatitis A vaccine site.

Pain at the injection site lasting more than 3 days was reported by 17.4% of subjects after ViATIM, by 2.8% of subjects for the monovalent Vi vaccine site and by 0.6% of subjects for the monovalent hepatitis A vaccine site.

Severe oedema/induration (> 5 cm) was reported in 7.9% of subjects at the ViATIM site. For subjects who received the two monovalent vaccines concomitantly at separate injection sites, severe oedema/induration was reported in 1.7% of subjects for both vaccine sites combined (in 1.1% of subjects at the Vi vaccine site and in 0.6% of subjects at the hepatitis A vaccine site).

The overall incidence of systemic reactions was similar between subjects who were vaccinated with ViATIM and subjects who received the two monovalent vaccines concomitantly at separate injection sites.

All reactions resolved without any sequelae.

Post marketing experience

Based on spontaneous reporting, the following additional adverse events have been reported during the commercial use of each monovalent vaccine.

Adverse reactions reported following the use of the monovalent purified Vi polysaccharide vaccine (and not listed above for ViATIM) include:

Immune system disorders

Very rare: anaphylactic/anaphylactoid reactions, including shock; serum sickness.

Nervous system disorders

Very rare: paraesthesia.

Respiratory, thoracic and mediastinal disorders

Very rare: aggravation of asthma.

Gastrointestinal disorders

Rare: vomiting, abdominal pain.

Skin and subcutaneous tissue disorders

Very rare: urticaria.

Adverse reactions reported following use of the monovalent inactivated hepatitis A vaccine (and not listed above for ViATIM) include:

Skin and subcutaneous tissue disorders

Very rare: urticaria.

General disorders and administration site conditions

Very rare: injection site nodule.

Investigations

Rare: transaminases increased (mild and reversible).

4.9 Overdose

No case of overdose has been reported.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Bacterial and viral vaccines combined, ATC code: J07C (combined) / P03 (Typhoid purified polysaccharide antigen) / C02 (Hepatitis A, inactivated, whole virus).

Four clinical studies provided useful data on immune responses to ViATIM. A total of 1090 subjects were included, with 179, 610, 243 and 58 subjects vaccinated in each study.

After the primary vaccination the seroprotection rate for HAV (%

The seroprotection rate for Vi (%

In one study that evaluated anti-Vi antigen seroprotection rates at years 1, 2 and 3 after the first dose of ViATIM and after re-vaccination with ViATIM at year 3, results were as follows:

	ViATIM
	Year 1	Year 2	Year 3	28 days after Re-vaccination at Year 3
Number of vaccinees	139	124	112	46
% of vaccinees seroprotected (95% CI)	44.6 (36.2-53.3)	40.3 (31.6-49.5)	32.1 (23.6-41.6)	69.6 (54.2-82.3)

Serological data show continuing protection against hepatitis A for up to 36 months in subjects who responded to the first dose of ViATIM. Anti-HAV antigen seroprotection rates at years 1, 2 and 3 after the first dose of ViATIM and after re-vaccination with ViATIM at year 3 were as follows:

	ViATIM
	Year 1	Year 2	Year 3	28 days after Re-vaccination at Year 3
Number of vaccinees	140	124	112	46
% (95% CI)	99.3 (96.1-100)	98.4 (94.3-99.8)	99.1 (95.1-100)	100 (92.3-100)

Similar results were seen at all timepoints in the control group who received concomitant monovalent purified Vi polysaccharide and inactivated hepatitis A vaccines.

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Non-clinical data obtained with this vaccine, or with the monovalent vaccines contained within this combined vaccine, reveal no special hazard for humans based on single, repeated dose and local tolerance toxicity studies.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Purified Vi polysaccharide typhoid vaccine component:

Phosphate buffer solution:

Sodium chloride

Disodium phosphate dihydrate

Sodium dihydrogen phosphate dihydrate

Water for Injections

Inactivated hepatitis A vaccine component:

2-Phenoxyethanol solution

Formaldehyde

Medium 199 Hanks (without phenol red)* supplemented with polysorbate 80

*Medium 199 Hanks (without phenol red) is a complex mixture of amino acids (including phenylalanine), mineral salts, vitamins and other components (including glucose), diluted in water for injections and pH adjusted with hydrochloric acid or sodium hydroxide

6.2 Incompatibilities

In the absence of compatibility studies, this vaccine must not be mixed with other vaccines or medicinal products.

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Store in a refrigerator (2°C - 8°C). Do not freeze. If frozen, the vaccine should be discarded.

Keep the vaccine in the outer carton in order to protect from light.

6.5 Nature And Contents Of Container

A prefilled syringe (type I glass) with a dual-chamber (0.5 millilitre of vaccine in each chamber) with elastomer (chlorobutyl and bromobutyl rubber blend) plunger-stopper, elastomer tip cap and elastomer by-pass stopper.

Pack of 1 or 10 prefilled syringes supplied with or without needle.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

The two vaccine components should only be mixed immediately prior to injection.

Shake before mixing and again prior to injection to obtain a homogeneous suspension. The contents of the two compartments are mixed by slowly advancing the plunger. The final volume to be injected is 1 millilitre.

The vaccine should be visually inspected before administration for any foreign particulate matter. The mixed vaccine is a cloudy, whitish suspension.

Any unused product or waste material should be disposed of in accordance with local requirements.

7. Marketing Authorisation Holder

Sanofi Pasteur MSD Ltd

Mallards Reach

Bridge Avenue

Maidenhead

Berkshire SL6 1QP

8. Marketing Authorisation Number(S)

PL 06745/0114

9. Date Of First Authorisation/Renewal Of The Authorisation

02/09/06

10. Date Of Revision Of The Text

09/2010

Vexol 1% Eye Drops, Suspension

1. Name Of The Medicinal Product

VEXOL 1% (10 mg/ml) eye drops, suspension

2. Qualitative And Quantitative Composition

Rimexolone 10 mg/ml.

For excipients, see section 6.1.

3. Pharmaceutical Form

Eye drops, suspension.

Vexol is a white to off-white suspension.

4. Clinical Particulars

4.1 Therapeutic Indications

VEXOL is indicated for the treatment of postoperative inflammation following ocular surgery, for the treatment of anterior uveitis, and for the treatment of corticosteroid responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe. The inflammation should be of a non-infectious nature. In more serious cases, and if the posterior part of the globe is affected, subconjunctival injection or systemic treatment is recommended (see section 4.4).

4.2 Posology And Method Of Administration

Postoperative Inflammation

Apply one drop of VEXOL into the conjunctival sac of the affected eye four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period. There are no clinical data on the use of VEXOL immediately after surgery.

Steroid Responsive Inflammation

Apply one drop of VEXOL into the conjunctival sac of the affected eye four times or more daily. The duration of treatment should be determined by the prescribing physician according to the severity of the disease, but should not exceed four weeks.

Uveitis

Apply one drop of VEXOL into the conjunctival sac of the affected eye every hour during the daytime for the first week, one drop every two hours during the daytime of the second week, four times per day during the third week; then twice per day during the first 4 days of week four and then once per day during the last 3 days of week four. Alternative dosing may be appropriate in some circumstances.

Use in elderly

Clinical studies have indicated that dosage modifications are not required for use in the elderly.

Use in children

Safety and effectiveness in children have not been established.

Use in hepatic and renal impairment

No clinical experience in patients with impaired renal or hepatic function is available.

Instructions for Use

Shake well before use. Do not touch dropper tip to any surface, as this may contaminate the suspension. Keep the bottle tightly closed when not in use.

4.3 Contraindications

Hypersensitivity to the active substance or any of the excipients.

VEXOL is contraindicated in epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and most other viral diseases of cornea and conjunctiva; mycobacterial infection of the eye; fungal diseases of the eye; acute purulent untreated infections which, like other diseases caused by microorganisms may be masked or enhanced by the presence of the steroid; red eye, where the diagnosis is unconfirmed; and amoebic infections.

4.4 Special Warnings And Precautions For Use

In more serious cases, and if the posterior part of the globe is affected, subconjunctival injection or treatment is recommended. But Vexol is not for injection. Prolonged use may result in ocular hypertension/glaucoma, damage to the optic nerve, defects in visual acuity and visual fields, and posterior subcapsular cataract formation. Prolonged use may also result in secondary ocular infections due to suppression of host response. Acute purulent infections of the eye may be masked or exacerbated by the presence of corticosteroid medication. In those diseases causing thinning of the cornea or sclera, perforation has been known to occur with topical steroids. It is advisable that the intraocular pressure be checked frequently.

General: Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been or is in use.

The wearing of contact lenses (hard or soft) is discouraged during treatment of an ocular inflammation. VEXOL should not be instilled while wearing contact lenses; lenses should not be inserted for 15 minutes after instillation of VEXOL. Additionally, the preservative benzalkonium chloride may cause eye irritation and is known to discolour soft lenses.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Specific drug interaction studies have not been conducted with VEXOL. No drug interactions were identified during the clinical development program.

If concomitant eye preparations are to be used, the patient should be advised to wait about 15 minutes between the two applications.

4.6 Pregnancy And Lactation

Pregnancy

There are no adequate data from the use of Vexol in pregnant women.

Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.

Vexol should not be used during pregnancy unless clearly necessary.

Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism.

Lactation

It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human breast milk. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman; a decision should be made whether to discontinue nursing or discontinue therapy, taking into consideration the importance of the drug to the mother.

4.7 Effects On Ability To Drive And Use Machines

Temporarily blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision or visual disturbances occur, the patient must wait until the vision clears before driving or using machinery.

4.8 Undesirable Effects

In clinical studies with Vexol, the most frequently reported adverse events and local symptoms were: blurred vision (2.6%) and ocular discharge (2.2%).

The following undesirable effects were reported during clinical trials with Vexol:

Infections and Infestations

Uncommon (

Nervous System Disorders

Uncommon (

Eye Disorders:

Common (

Vascular Disorders

Uncommon (

Investigations:

Common (

Uncommon (

In post-marketing experience, the most frequently reported events are eye irritation, lid margin crusting, ocular hyperaemia and intraocular pressure increase. These events are similar to those identified during clinical trials.

Use of topical corticosteroids may cause increased intraocular pressure (see section 4.4).

4.9 Overdose

A topical overdose is not likely to be associated with toxicity. A topical overdosage of VEXOL may be flushed from the eye(s) with luke warm tap water.

Accidental oral ingestion is also unlikely to be associated with toxicity. Treatment of a suspected ingestion is symptomatic and supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: SO1BA13: Ophthalmological anti-inflammatory corticosteroid.

Corticosteroids suppress the inflammatory response to a variety of inciting agents of a mechanical, chemical, or immunological nature. They prevent or suppress redness, swelling, tenderness, exudation, cellular infiltration, capillary dilatation, fibroblastic proliferation, deposition of collagen and late cicatrization. Placebo controlled clinical studies demonstrated that VEXOL is efficacious for the treatment of anterior chamber inflammation following cataract surgery.

In two controlled clinical trials, VEXOL demonstrated clinical and statistical equivalence to 1% prednisolone acetate in controlling uvetic inflammation. Supportive studies have confirmed the anti-inflammatory activity of VEXOL in steroid responsive ocular inflammation.

Corticosteroids are capable of producing a rise in intraocular pressure in susceptible individuals. In a controlled 6 week study of steroid responsive subjects the time to raise intraocular pressure was similar to VEXOL and 0.1% fluorometholone given four times daily.

5.2 Pharmacokinetic Properties

As with other topically administered drugs, VEXOL is absorbed systemically. Studies in normal volunteers dosed bilaterally once every hour during waking hours for one week have demonstrated maximal serum concentrations ranging from less than 80 pg/ml to approximately 460 pg/ml. The mean maximal serum concentrations were approximately 150 pg/ml (n = 15). Serum concentrations were at or near steady state on day one of the dosing regimen. After decreasing the dosing frequency to once every two hours while awake during the second week of administration, mean maximal serum concentrations were approximately 100 pg/ml. The serum half-life of rimexolone could not be reliably estimated due to the large number of samples below the quantitation limit of the assay (80 pg/ml). However, based on the time required to reach steady-state, the half-life appears to be short (1 - 2 hours).

Based upon in vivo and in vitro preclinical metabolism studies and on in vitro results with human liver preparations, Rimexolone undergoes extensive metabolism with primary

(> 80%) excretion via the faeces. Metabolites have been shown to be less active than parent drug, or inactive in human glucocorticoid binding assays.

5.3 Preclinical Safety Data

Carcinogenesis, mutagenesis, impairment of fertility: Rimexolone has been shown to be not mutagenic in a battery of in vitro and in vivo mutagenicity assays. Fertility and reproductive capability was not impaired in a study in rats with plasma levels (42 nanograms/ml) approximately 200 times those obtained in clinical studies after topical administration (<0.2 nanogram/ml). Long-term studies have not been conducted in animals to evaluate the carcinogenic potential of rimexolone.

Rimexolone has been shown to be teratogenic and embryotoxic in rabbits following subcutaneous administration, but was not teratogenic or embryotoxic in rats. Corticosteroids are recognised to cause foetal resorptions and malformations in animals, though the association in humans has not been firmly established.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzalkonium chloride ,

Mannitol

Carbomer,

Polysorbate 80,

Sodium chloride,

Disodium edetate,

Sodium hydroxide and/or hydrochloric acid

Purified water.

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

1 year for the 3 mL bottle.

2 years for the 5 mL and 10 mL bottles.

In use shelf life - one month after first opening.

6.4 Special Precautions For Storage

Do not store above 30C. Do not freeze.

6.5 Nature And Contents Of Container

Low density polyethylene bottles (droptainer) containing 3ml, 5ml or 10ml and with polypropylene screw caps.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Alcon Laboratories (UK) Limited,

Pentagon Park,

Boundary Way

Hemel Hempstead,

Hertfordshire,

HP2 7UD

United Kingdom

8. Marketing Authorisation Number(S)

PL 00649/0136

9. Date Of First Authorisation/Renewal Of The Authorisation

26/09/2005

10. Date Of Revision Of The Text

26 /09/2005

Vicks Cough Syrup for Chesty Coughs

1. Name Of The Medicinal Product

Vicks Cough Syrup for Chesty Coughs

2. Qualitative And Quantitative Composition

ACTIVE INGREDIENTS

	%w/v	Specification
Guaifenesin	1.333	Ph. Eur.

3. Pharmaceutical Form

Syrup for oral administration.

4. Clinical Particulars

4.1 Therapeutic Indications

To relieve a cough, loosen mucus, soothe and coat the throat and make the cough more productive.

4.2 Posology And Method Of Administration

Adults and children 12 years and over: 3 x 5ml spoonfuls

Repeat every 4 hours as needed.

No more than 6 doses a day

4.3 Contraindications

Not to be used in children under the age of 6 years

Known hypersensitivity to guaifenesin.

4.4 Special Warnings And Precautions For Use

Do not exceed the stated dose.

Do not administer to children under 2 years except on medical advice.

If symptoms persist, consult your doctor.

Keep out of reach of children.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known.

4.6 Pregnancy And Lactation

There is no literature evidence of hazard due to guaifenesin but, as with all medicines, use is not recommended during the first trimester and during breast feeding.

4.7 Effects On Ability To Drive And Use Machines

None expected.

4.8 Undesirable Effects

Gastrointestinal discomfort has been reported.

4.9 Overdose

4.9.1 Symptoms

Symptoms of very large overdose include nausea and vomiting. Any absorbed guaifenesin is, however, rapidly metabolised and excreted in the urine.

4.9.2 Management of an overdose

Treatment is supportive and symptomatic.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Guaifenesin has an expectorant action which increases the output of the respiratory tract fluid by reducing surface tension. The increased flow of less viscid secretions promotes cilary action and facilitates the removal of mucous.

5.2 Pharmacokinetic Properties

Guaifenesin is absorbed from the gastrointestinal tract. It is metabolised and excreted in the urine.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance which are additional to that already included in the other sections of the SmPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sucrose.

Sodium saccharin.

Propylene glycol.

Ethanol 96%.

Sodium citrate, hydrous.

Citric acid, anhydrous.

Carboxymethylcellulose sodium.

Polyethylene oxide.

Flavour 9512 (David Michael Heat)

Black cherry flavour RF 1195.

Levomenthol.

Menthoxypropanediol (TK10).

Macrogol stearate 40.

Sodium benzoate.

CI 16255 Acid red 18 (E124 Ponceau 4R).

Purified water.

6.2 Incompatibilities

None known.

6.3 Shelf Life

Shelf life (unopened): 3 years

6.4 Special Precautions For Storage

Do not store above 25^oC.

6.5 Nature And Contents Of Container

Amber cylindrical glass bottle (pharmaceutical type III) with a Crab claw seal (polypropylene) child resistant closure:

Bottles containing 15ml, 30ml, 100ml, 120ml, 180ml of product are available

6.6 Special Precautions For Disposal And Other Handling

No specific instructions required.

7. Marketing Authorisation Holder

Procter & Gamble (Health & Beauty Care) Ltd.,

The Heights,

Brooklands,

Weybridge,

Surrey,

KT13 0XP.

8. Marketing Authorisation Number(S)

PL 0129/0078

9. Date Of First Authorisation/Renewal Of The Authorisation

19 June 1996

10. Date Of Revision Of The Text

Oct 2009

Volsaid Retard 75mg & 100mg tablets

Volsaid Retard 75 mg & 100 mg Tablets

diclofenac sodium

Important things you need to know about Volsaid

• Volsaid is a non-steroidal anti-inflammatory medicine, prescribed to reduce swelling and ease inflammation in conditions affecting the joints and muscles.


• You need to take it regularly to get the maximum benefit. Do not stop taking it without talking to your doctor.


• Volsaid can cause serious side effects in some people (read Section 4 for details). If you experience difficulty in breathing, an allergic reaction such as skin rashes, signs of bleeding from your intestines or vomit blood contact your doctor immediately.


• If you are elderly, suffer from kidney, liver or heart problems, your doctor may regularly monitor your condition to check you are taking the correct dose of Volsaid.


• Taking other medicines, including other NSAIDs, may sometimes cause problems. Check with your doctor or pharmacist before taking any other medicines.


• If you are (or might become) pregnant while taking Volsaid, it is important to talk to your doctor about this.

Now read the rest of this leaflet. It includes other important information on the safe use of this medicine that might be especially important for you. This leaflet was last updated on 01/2010.

In this leaflet:

• 1. What Volsaid is and what it is used for


• 2. Before you take Volsaid


• 3. How to take Volsaid


• 4. Possible side effects


• 5. How to store Volsaid


• 6. Further information

What Volsaid is and what it is used for

Volsaid Retard Tablets contain diclofenac sodium which belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs) that reduce pain and inflammation. They are called modified release tablets because they are manufactured in a way that allows the diclofenac sodium to be released and slowly absorbed by the body over a period of several hours.

Volsaid Retard Tablets relieve pain, reduce swelling and ease inflammation in the following conditions affecting the joints and muscles:

• rheumatoid arthritis, osteoarthritis, ankylosing spondylitis (form of spinal arthritis), acute gout


• low backache, sprains and strains, soft tissue sports injuries, frozen shoulder, dislocations and fractures


• conditions affecting the tendons, e.g. tendonitis, tenosynovitis, bursitis

They are also used to treat pain and inflammation associated with orthopaedic, dental and other minor surgery.

Before you take Volsaid

Do not take Volsaid:

• if you are allergic to diclofenac sodium, aspirin, ibuprofen, any other NSAID or any of the other ingredients in the tablets (these are listed in section 6, Further Information) Signs of an allergic reaction include breathing problems, a runny nose, swelling of the face or throat, or a skin rash


• if you have now, or ever had, a peptic ulcer (ulcer in your stomach or duodenum) or bleeding in your stomach, or have had two or more episodes of peptic ulcers, stomach bleeding or perforation


• if you have had stomach or bowel problems after you have taken other NSAIDs


• if you suffer from porphyria, an inherited blood disorder that can cause increased sensitivity to light


• if you have severe heart failure, liver or kidney failure


• if you are in the last trimester of your pregnancy.

Take special care with Volsaid and always tell your doctor if:

• you have kidney or liver problems


• you suffer from Crohn’s disease or any other disease of the bowel or intestine


• you have recently undergone major surgery


• you have a history of any blood or bleeding disorder


• you have, or have ever suffered from asthma


• you have heart problems, previously had a stroke or think that you might be at risk of these conditions, (for example, if you have high blood pressure, diabetes or high cholesterol or are a smoker)


• if you have Lupus (SLE) or any similar condition


• if you are in the first six months of your pregnancy


• you are planning to become pregnant or if you have problems becoming pregnant.
  
  Volsaid may make it more difficult to become pregnant.

Medicines such as Volsaid may be associated with a small increased risk of heart attack or stroke. Any risk is more likely with high doses and prolonged treatment. Do not exceed the recommended dose or duration of treatment.

If you are elderly, suffer from kidney, liver or heart problems or have been taking this medicine or similar NSAIDs for a long time, your doctor may want to perform regular tests to monitor your condition and may need to carry out blood tests from time to time.

Taking other medicines

Before starting treatment, please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. If you have to go to a doctor, dentist or hospital for any reason, tell them that you are taking Volsaid.

In particular, tell your doctor if you are taking:

• lithium or medicines known as SSRIs, to treat depression


• methotrexate, to treat some inflammatory diseases and cancers


• aspirin, ibuprofen or tacrolimus, any other NSAIDs or COX-2(cyclo-oxygenase-2) inhibitor


• ciclosporin, to treat some inflammatory diseases and after transplants


• quinolone antibiotics, such as ciprofloxacin to treat bacterial infections


• water tablets (diuretics), such as amiloride


• anticoagulants, such as warfarin, to stop the blood clotting


• medicines to treat diabetes, such as gliclazide


• aminoglycosides, such as gentamycin to treat bacterial infections


• probenecid, to treat gout


• medicines to treat high blood pressure, such as beta-blockers


• cardiac glycosides, such as digoxin to treat heart problems


• mifepristone, used to terminate pregnancy


• oral steroids, such as prednisolone


• zidovudine, used to treat viral infections


• anti-platelet agents such as aspirin, used to reduce the formation of blood clots.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, or could become pregnant, talk to your doctor before taking your tablets.

Driving and using machines:

If you experience headaches, blurred vision, dizziness or drowsiness after taking these tablets, then do not drive or operate machinery.

How to take Volsaid

Always take your tablets exactly as your doctor has told you to. You should check with your doctor or pharmacist if you are not sure.

Dosage

• Volsaid is formulated so that you only have to take your tablets once or twice a day. This depends on which strength tablet you are taking. The label on the carton will tell you how many tablets you should take and when.


• Take your tablets at the same time each day, with or after food.


• Swallow your tablets whole, do not break or chew your tablets.


• Do not stop treatment even if you feel better unless told to do so by your doctor.

Adults and the elderly

• Volsaid Retard 75 mg tablet

The usual daily dose is one tablet once or twice a day. If you are taking your tablets twice a day, it is important that the second dose is taken 12 hours after the first dose and that no more than 2 tablets are taken in any 24 hour period.

• Volsaid Retard 100 mg tablet

The usual daily dose is one tablet once a day.

If you are elderly and are frail or have a low body weight your doctor will prescribe the lowest effective dose for you to take. Your doctor may want to monitor you for any bleeding from your stomach during the first four weeks of your treatment and may need to carry out blood tests from time to time.

Children must not take this medicine.

If you take more Volsaid than you should

If you accidentally take more Volsaid than you should, contact your nearest casualty department or tell your doctor or pharmacist immediately. Remember to take the pack and any remaining tablets with you.

If you forget to take Volsaid

Do not worry. Simply leave out that dose completely and then take your next dose at the right time. Do not take a double dose to make up for a missed dose.

Possible side effects

Like all medicines, Volsaid can cause side effects, although not everyone gets them.

Allergic reactions have been reported. If you experience any of these, contact your doctor or nearest casualty department immediately.

• tight chest, severe difficulty breathing or anaphylaxis where symptoms may be a rapid pulse, profuse sweating, fever and if severe, shock and collapse


• skin rashes, a serious illness with blistering of the skin, mouth, eyes and genitals (Stevens-Johnson Syndrome), itching, "nettle" rash or hives, a serious reaction causing swelling of the face or throat, unusual bruising, peeling, scaling, blistering and hair loss

If you experience any of the following serious side effects stop taking your tablets and contact your doctor or nearest casualty department immediately.

• perforation or ulcers of the stomach or small intestine


• vomiting blood or dark particles that look like coffee grounds


• lesions on the gullet


• blood in the stools or bloody diarrhoea


• worsening of Crohn’s disease or ulcerative colitis


• indigestion or heartburn


• pass black or tarry stools


• inflammation of the tongue, pancreas or stomach lining


• abdominal pain (pains in your stomach) or other abnormal stomach symptoms

The following side effects have also been reported, tell your doctor or pharmacist if you notice any of these:

• sensitivity to sunlight


• headache


• tiredness and drowsiness


• dizziness or “spinning”


• impaired hearing


• ringing in the ears


• difficulty in sleeping


• fits


• irritability


• anxiety


• depression


• confusion


• hallucinations


• tremors


• impaired memory


• loss of feeling


• feeling disorientated


• blurred vision


• constipation


• mouth ulcers


• nightmares


• changes in the way your kidneys work, including kidney failure


• presence of blood in your urine


• changes in liver function that may cause yellowing of the skin or eyes or affect the results from liver function tests


• reduction in red blood cells which can make the skin pale and cause weakness or breathlessness


• severe reduction in white blood cells which makes infections more likely


• fever


• reduction in blood platelets which increases risk of bleeding or bruising


• feeling your heartbeat


• severe reduction in blood cells which can cause weakness, bruising or make infections more likely


• high or low blood pressure


• impotence


• chest pain


• painful inflammation of the optic nerve in your eye


• feeling sick


• diarrhoea


• changes in taste


• flatulence


• loss of appetite


• stiff neck

Medicines such as Volsaid may be accociated with a small increased risk of heart attack (“myocardial infarction”) or stroke.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Volsaid

• Keep out of the reach and sight of children.


• Do not use Volsaid after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of that month.


• Do not store above 25ºC. Store in the original packaging.


• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

Further Information

What Volsaid contains:

The active substance in your tablets is diclofenac sodium. Each tablet contains 75 mg or 100 mg of diclofenac sodium.

The other ingredients are talc, ethylcellulose, magnesium stearate, povidone, stearic acid, hypromellose (E464), diethyl phthalate, macrogol 4000, titanium dioxide (E171), red iron oxide (E172) and yellow iron oxide (E172).

What Volsaid looks like and the contents of the pack:

Volsaid Retard 75 mg tablets are white, triangular tablets, marked with ‘DIC 75’ on one side.

Volsaid Retard 100 mg tablets are pale red, round, biconvex tablets, marked with ‘DIC 100’ on one side. They are packed in blister packs of 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000 tablets. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

The Marketing Authorisation holder and manufacturer is

Chiesi Limited

Cheadle Royal Business Park

Highfield

Cheadle

SK8 3GY

UK

Is this leaflet hard to see or read? Phone 0161 488 5555 for help.

00267 V6 / CP0010/2

Vitamin E Suspension 100mg / ml (Cambridge Laboratories)

1. Name Of The Medicinal Product

Vitamin E Suspension 100mg/ml

2. Qualitative And Quantitative Composition

Each 5ml of suspension contains 500mg of DL-alpha-tocopheryl acetate.

3. Pharmaceutical Form

Oral Suspension

4. Clinical Particulars

4.1 Therapeutic Indications

For the correction of Vitamin E deficiency occurring in malabsorption disorders ie. cystic fibrosis, chronic cholestasis and abetalipoproteinaemia.

4.2 Posology And Method Of Administration

Route of administration: For oral use.

Adults (including the elderly)

For the treatment of malabsorption disorders the following doses should be administered:

Cystic fibrosis 100-200mg/day

Abetalipoproteinaemia 50-100mg/kg/day

Children

For the treatment of cystic fibrosis a dose of 50mg/day should be given to children less than 1 year and 100mg/day to children 1 year and over.

The adult dosage should be used for the treatment of abetalipoproteinaemia (50-100mg/kg/day).

Infants with vitamin E deficiency which is secondary to chronic cholestasis may be treated with doses of 150-200mg/kg/day.

4.3 Contraindications

Use in patients with a known hypersensitivity to Vitamin E.

4.4 Special Warnings And Precautions For Use

Vitamin E has been reported to increase the risk of thrombosis in patients predisposed to this condition, including patients taking oestrogens. This finding has not been confirmed but should be borne in mind when selecting patients for treatment, in particular women taking oral contraceptives containing oestrogens.

A higher incidence of necrotising enterocolitis has been noted in lower weight premature infants (less than 1.5kg) treated with vitamin E.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Vitamin E may increase the risk of thrombosis in patients taking oestrogens (see 4.4 above).

4.6 Pregnancy And Lactation

There is no evidence of the safety of high doses of vitamin E in pregnancy nor is there evidence from animal work that it is free from hazard, therefore do not use in pregnancy especially in the first trimester. No information is available on excretion in breast milk, therefore it is advisable not to use during lactation.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Diarrhoea and abdominal pain may occur with doses greater than 1g daily.

4.9 Overdose

Transient gastro-intestinal disturbances have been reported with doses greater than 1g daily and where necessary, general supportive measures should be employed.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

The exact role of vitamin E in the animal organism has not yet been established. Vitamin E is known to exert an important physiological function as an antioxidant for fats, with a sparing action on vitamin A, carotenoids and on unsaturated fatty acids. Other work has demonstrated that vitamin E is connected with the maintenance of certain factors essential for the normal metabolic cycle.

5.2 Pharmacokinetic Properties

Vitamin E is absorbed from the gastrointestinal tract. Most of the vitamin appears in the lymph and is then widely distributed to all tissues. Most of the dose is slowly excreted in the bile and the remainder is eliminated in the urine as glucuronides of tocopheronic acid or other metabolites.

5.3 Preclinical Safety Data

There are no pre-clinical 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

Castor oil polyethylene glycol ether

Benzoic acid

Sorbic acid

Glycerol

Syrup

Flavour raspberry

Purified Water

6.2 Incompatibilities

None.

6.3 Shelf Life

Unopened: Two years.

After first opening: One month (The product will be stable after opening for the normal duration of treatment providing the cap is replaced after use and the recommended storage conditions on the label are observed).

6.4 Special Precautions For Storage

Store below 25°C.

6.5 Nature And Contents Of Container

Amber glass bottles with aluminium screw caps or Vistop tamper-evident caps.

6.6 Special Precautions For Disposal And Other Handling

Vitamin E Suspension may be diluted with Syrup BP but should be used immediately and not stored.

7. Marketing Authorisation Holder

Cambridge Laboratories Limited

Deltic House

Kingfisher Way

Silverlink Business Park

Wallsend

Tyne & Wear

NE28 9NX

8. Marketing Authorisation Number(S)

PL 12070/0010

9. Date Of First Authorisation/Renewal Of The Authorisation

8 March 1993

10. Date Of Revision Of The Text

March 2000

Voltarol Dispersible Tablets 50mg

VOLTAROL Dispersible Tablets 50 mg

(diclofenac sodium)

What you need to know about Voltarol Dispersible Tablets

Your doctor has decided that you need this medicine to help treat your condition.

Please read this leaflet carefully before you start to take your medicine. It contains important information. Keep the leaflet in a safe place because you may want to read it again.

If you have any other questions, or if there is something you don’t understand, please ask your doctor or pharmacist.

This medicine has been prescribed for you. Never give it to someone else. It may not be the right medicine for them even if their symptoms seem to be the same as yours.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Voltarol Dispersible Tablets are, and what they are used for


• 2. Things to consider before you start to take Voltarol Dispersible Tablets


• 3. How to take Voltarol Dispersible Tablets


• 4. Possible side effects


• 5. How to store Voltarol Dispersible Tablets


• 6. Further information

What Voltarol Dispersible Tablets are, and what they are used for

Diclofenac sodium, the active ingredient in Voltarol Dispersible Tablets, is one of a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs reduce pain and inflammation.

Voltarol Dispersible Tablets act quickly and so are used to treat short term painful conditions affecting the joints and muscles. They are especially useful for the treatment of sprains, strains and back pain. They should not be taken for more than three months.

Things to consider before you start to take Voltarol Dispersible Tablets

Some people MUST NOT take Voltarol Dispersible Tablets. Talk to your doctor if:

• you think you may be allergic to diclofenac sodium, aspirin, ibuprofen or any other NSAID, or to any of the other ingredients of Voltarol Dispersible Tablets. (These are listed at the end of the leaflet.) Signs of a hypersensitivity reaction include swelling of the face and mouth (angioedema), breathing problems, runny nose, skin rash or any other allergic type reaction


• you have now, or have ever had, a stomach (gastric) or duodenal (peptic) ulcer, or bleeding in the digestive tract (this can include blood in vomit, bleeding when emptying bowels, fresh blood in faeces or black, tarry faeces)


• you have had stomach or bowel problems after you have taken other NSAIDs


• you have severe heart, kidney or liver failure


• you are more than six months pregnant.

You should also ask yourself these questions before taking Voltarol Dispersible Tablets:

• Do you suffer from any stomach or bowel disorders including ulcerative colitis or Crohn's disease?


• Do you have kidney or liver problems, or are you elderly?


• Do you have a condition called porphyria?


• Do you suffer from any blood or bleeding disorder? If you do, your doctor may ask you to go for regular check-ups while you are taking these tablets.


• Have you ever had asthma?


• Are you breast-feeding?


• Do you have heart problems, or have you had a stroke, or do you think you might be at risk of these conditions (for example, if you have high blood pressure, diabetes, or high cholesterol or are you a smoker)?


• Do you have Lupus (SLE) or any similar condition?

If the answer to any of these questions is YES, discuss your treatment with your doctor or pharmacist because Voltarol Dispersible Tablets might not be the right medicine for you.

Are you taking other medicines?

Some medicines can interfere with your treatment. Tell your doctor or pharmacist if you are taking any of the following:

• Medicines to treat diabetes


• Anticoagulants (blood thinning tablets like warfarin)


• Diuretics (water tablets)


• Lithium (used to treat some mental problems)


• Methotrexate (for some inflammatory diseases and some cancers)


• Ciclosporin or tacrolimus (used to treat some inflammatory diseases and after transplants)


• Quinolone antibiotics (for infections)


• Any other NSAID or COX-2 (cyclo-oxgenase-2) inhibitor, for example aspirin or ibuprofen


• Mifepristone (a medicine used to terminate pregnancy)


• Cardiac glycosides (for example digoxin), used to treat heart problems


• Medicines known as SSRIs used to treat depression


• Oral steroids (an anti-inflammatory drug)


• Medicines used to treat heart conditions or high blood pressure, for example beta-blockers or ACE inhibitors.

Always tell your doctor or pharmacist about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Pregnancy

• Are you pregnant or planning to become pregnant? Although not common, abnormalities have been reported in babies whose mothers have taken NSAIDs during pregnancy. You should not take Voltarol Dispersible Tablets during the last 3 months of pregnancy as it may affect the baby’s circulation.


• Are you trying for a baby? Taking Voltarol Dispersible Tablets may make it more difficult to conceive. You should talk to your doctor if you are planning to become pregnant, or if you have problems getting pregnant.

Will there be any problems with driving or using machinery?

Very occasionally people have reported that Voltarol Dispersible Tablets have made them feel dizzy, tired or sleepy. Problems with eyesight have also been reported. If you are affected in this way, you should not drive or operate machinery.

Other special warnings

• You should take the lowest dose of Voltarol Dispersible Tablets for the shortest possible time, particularly if you are underweight or elderly.


• There is a small increased risk of heart attack or stroke when you are taking any medicine like Voltarol. The risk is higher if you are taking high doses for a long time. Always follow the doctor’s instructions on how much to take and how long to take it for.


• Whilst you are taking these medicines your doctor may want to give you a check-up from time to time.


• If you have a history of stomach problems when you are taking NSAIDs, particularly if you are elderly, you must tell your doctor straight away if you notice any unusual symptoms.


• Because it is an anti-inflammatory medicine, Voltarol Dispersible Tablets may reduce the symptoms of infection, for example headache, and high temperature. If you feel unwell and need to see a doctor, remember to tell him or her that you are taking Voltarol Dispersible Tablets.


• Voltarol Dispersible Tablets are not suitable for children.


• The tablets contain erythrosine and may be unsuitable for some people.

How to take Voltarol Dispersible Tablets

The doctor will tell you how many Voltarol Dispersible Tablets to take and when to take them. Always follow his/her instructions carefully. The dose will be on the pharmacist’s label. Check the label carefully. If you are not sure, ask your doctor or pharmacist. Keep taking your tablets for as long as you have been told, unless you have any problems. In that case, check with your doctor.

Take the tablets before or with food.

Drop the tablets into a glass of water, and stir. Drink the pink, blackcurrant-flavoured liquid at once. To make sure you get all of the medicine, rinse the glass round with a small amount of water and drink this as well.

The usual doses are:

Adults

One tablet two or three times a day.

Elderly

Your doctor may advise you to take a dose that is lower than the usual adult dose if you are elderly. Your doctor may also want to check closely that the Voltarol Dispersible Tablets are not affecting your stomach.

These tablets are not suitable for children.

The doctor may also prescribe another drug to protect the stomach to be taken at the same time, particularly if you have had stomach problems before, or if you are elderly, or taking certain other drugs as well.

What if you forget to take a dose?

If you forget to take a dose, take one as soon as you remember. If it is nearly time for your next dose, though, just take the next dose and forget about the one you missed. Do not double up on the next dose to make up for the one missed. Do not take more than 150 mg (three tablets) in 24 hours.

What if you take too many tablets?

If you, or anyone else, accidentally takes too much, tell your doctor or your nearest hospital casualty department. Take your medicine pack with you so that people can see what you have taken.

Possible side effects

Voltarol Dispersible Tablets are suitable for most people, but, like all medicines, they can sometimes cause side effects.

Some side effects can be serious

Stop taking Voltarol Dispersible Tablets and tell your doctor straight away if you notice:

• Stomach pain, indigestion, heartburn, wind, nausea (feeling sick) or vomiting (being sick)


• Any sign of bleeding in the stomach or intestine, for example, when emptying your bowels, blood in vomit or black, tarry faeces


• Allergic reactions which can include skin rash, itching, bruising, painful red areas, peeling or blistering


• Wheezing or shortness of breath (bronchospasm)


• Swollen face, lips, hands or fingers


• Yellowing of your skin or the whites of your eyes


• Persistent sore throat or high temperature


• An unexpected change in the amount of urine produced and/or its appearance.

If you notice that you are bruising more easily than usual or have frequent sore throats or infections, tell your doctor.

The side effects listed below have also been reported.

Up to 1 in 10 people have experienced:

• Stomach pain, heartburn, nausea, vomiting, diarrhoea, indigestion, wind, loss of appetite


• Headache, dizziness, vertigo


• Skin rash or spots


• Raised levels of liver enzymes in the blood

Between 1 in 100,000 and 1 in 100 people have experienced:

• Stomach ulcers or bleeding (there have been very rare reported cases resulting in death, particularly in the elderly)


• Drowsiness, tiredness


• Hypotension (low blood pressure, symptoms of which may include faintness, giddiness or light headedness)


• Skin rash and itching


• Fluid retention, symptoms of which include swollen ankles


• Liver function disorders, including hepatitis and jaundice

Isolated side-effects, reported in less than 1 in 100,000 people include:

Effects on the nervous system:

Tingling or numbness in the fingers, tremor, blurred or double vision, hearing loss or impairment, tinnitus (ringing in the ears), sleeplessness, nightmares, mood changes, depression, anxiety, mental disorders, confusion, hallucinations, malaise, disorientation and loss of memory, fits, headaches together with a dislike of bright lights, fever and a stiff neck, disturbances in sensation.

Effects on the stomach and digestive system:

Constipation, inflammation of the tongue, mouth ulcers, taste changes, lower gut disorders (including inflammation of the colon).

Effects on the heart, chest or blood:

Palpitations (fast or irregular heart beat), chest pain, hypertension (high blood pressure), inflammation of blood vessels (vasculitis), inflammation of the lung (pneumonitis), congestive heart failure, blood disorders (including anaemia), heart attack, stroke.

Effects on the liver or kidneys:

Kidney or liver disorders, presence of blood or protein in the urine.

Effects on skin or hair:

Serious skin rashes including Stevens-Johnson syndrome and Lyell’s syndrome and other skin rashes which may be made worse by exposure to sunlight.

Hair loss.

Other effects:

Inflammation of the pancreas, impotence.

Medicines such as diclofenac may be associated with a small increased risk of heart attack or stroke.

Do not be alarmed by this list - most people take Voltarol Dispersible Tablets without any problems.

If any of the symptoms become troublesome, or if you notice anything else not mentioned here, please go and see your doctor. He/she may want to give you a different medicine.

How to store Voltarol Dispersible Tablets

Store in a dry place, below 30°C. Keep the tablets in their original pack.

Keep out of the reach and sight of children.

Do not take Voltarol Dispersible Tablets after the expiry date which is printed on the outside of the pack.

If your doctor tells you to stop taking the tablets, please take any unused tablets back to your pharmacist to be destroyed. Do not throw them away with your normal household water or waste. This will help to protect the environment.

Further information

Voltarol Dispersible Tablets contain 50 mg of the active ingredient, diclofenac sodium. The tablets also contain the inactive ingredients avicel, croscarmellose sodium, sodium starch glycollate, sodium saccharin, hydrogenated castor oil, talc, aerosol, blackcurrant flavouring and red colouring.

They come in aluminium blister packs containing either 3 or 21 tablets. Not all of the pack sizes may be marketed.

The Product licence holder is

Novartis Pharmaceuticals UK Limited

trading as Geigy Pharmaceuticals

Frimley Business Park

Frimley

Camberley

Surrey

GU16 7SR

England

Voltarol Dispersible Tablets are released on to the market by

Novartis Pharmaceuticals UK Limited

Horsham

West Sussex

RH12 5AB

England

This leaflet was revised in January 2009

If you would like any more information, or would like the leaflet in a different format, please contact Medical Information at Novartis Pharmaceuticals UK Ltd, telephone number 01276 698370.

VOLTAROL is a registered trade mark

Copyright Novartis Pharmaceuticals UK Limited

Viazem XL 360mg

1. Name Of The Medicinal Product

VIAZEM XL

2. Qualitative And Quantitative Composition

Diltiazem hydrochloride: 360 mg capsule.

For excipients see section 6.1

3. Pharmaceutical Form

Prolonged release capsule, hard.

Blue-green opaque capsules. Each capsule is printed on the cap and body, in white ink, with Viazem XL 360.

4. Clinical Particulars

4.1 Therapeutic Indications

VIAZEM XL is indicated for the management of stable angina pectoris and the treatment of mild to moderate hypertension.

4.2 Posology And Method Of Administration

Dosage requirements may differ between patients with angina and patients with hypertension. In addition individual patients response may vary, necessitating careful titration. The range of strengths facilitates titration to the optimal dose.

One capsule of VIAZEM XL is to be taken before or during a meal. The dose should be taken at approximately the same time each day.

The capsule should not be chewed but swallowed whole, with a glass of water.

Due to the variability of release profile in individual patients, when changing from one type of sustained release diltiazem preparation to another, it may be necessary to adjust the dose.

Adults:

Hypertension: The usual starting dose is 180 mg once daily. The dose may be increased after 2-4 weeks according to the patient's response and the usual maintenance dose is 240mg-360mg once daily. The maximum daily dose is 360 mg. However, the single daily doses of 300 mg and 360 mg should only be administered to patients when no satisfactory therapeutic effect has been effected with lower doses and after the benefit risk-ratio has been carefully assessed by the doctor.

Angina: Care should be taken when titrating patients with stable angina in order to establish the optimal dose. The usual starting dose is 180 mg once daily. The dose may be increased after 2-4 weeks according to the patient's response. The maximum daily dose is 360 mg. However, the single daily doses of 300 mg and 360 mg should only be administered to patients when no satisfactory therapeutic effect has been effected with lower doses and after the benefit risk-ratio has been carefully assessed by the doctor.

Elderly and patients with impaired hepatic or renal function:

Plasma levels of diltiazem can be increased in the elderly, and in patients with impaired hepatic renal or hepatic function. In these cases, the starting dose should be one 120mg VIAZEM XL capsule once daily. Heart rate should be monitored and if it falls below 50 beats per minute, the dose should not be increased. Dose adjustment may be required to obtain a satisfactory clinical response.

Children:

Safety and efficacy in children have not been established.

4.3 Contraindications

Diltiazem depresses atrioventricular node conduction and is therefore contraindicated in patients with severe bradycardia (less than 50 bpm), sick sinus syndrome, congestive heart failure, and left ventricular failure with second or third degree AV or sino-atrial block, except in the presence of a functioning pacemaker. Diltiazem is also contraindicated in left ventricular failure with pulmonary stasis as diltiazem may have mild negative effects on contractility.

Diltiazem is contraindicated in acute complicated myocardial infarction (e.g. bradycardia hypotension, congestive heart failure/reduced LV function), pulmonary congestion, hypotension (<90 mmHg systolic) cerebrovascular accident, cardiac shock and unstable angina pectoris.

Diltiazem is contraindicated in pre-excitation syndrome (e.g. WPW) accompanied with atrial flutter, fibrillation and in digitalis intoxication, as diltiazem may precipitate ventricular tachycardia.

Diltiazem should not be used in patients with known hypersensitivity to diltiazem.

Diltiazem should not be used during pregnancy, by women of child-bearing potential, or by women who are breastfeeding.

4.4 Special Warnings And Precautions For Use

Patients treated with beta-adrenoreceptor blocking drugs and patients with conduction disturbances (bradycardia, bundle branch block, first degree AV block, prolonged PR interval) should only be treated with VIAZEM XL after special consideration due to the risk of serious bradyarrhythmias.

This product should be used with caution in patients with hepatic dysfunction. Abnormalities of liver function may appear during therapy. The higher single daily doses of VIAZEM XL capsules 300mg and 360mg should not be administered to patients with impaired renal and/or hepatic function and to elderly patients (prolonged half life of elimination) because there is no experience on the use of such high dosages in these patient categories.

In patients undergoing long-term therapy with cyclosporin, plasma levels of cyclosporin should be monitored when concurrent administration of diltiazem is initiated, or discontinued or if the dose of diltiazem is changed.

Abnormally short transit time through the gastrointestinal tract could lead to incomplete release of contents of the capsule e.g. in chronic conditions with associated diarrhoea such as Crohns disease or ulcerative colitis.

Patients with rare heriditary problems of fructose intolerances, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicines.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Combinations contraindicated as a safety measure:

In animals, fatal ventricular fibrillations are constantly seen during administration of verapamil and dantrolene via the i.v. route. The combination of a calcium antagonist and dantrolene is therefore potentially dangerous. The concurrent iv administration of beta-adrenergic blocking agents with diltiazem should be avoided because an additive effect on SA and AV conduction and ventricular function will occur. The use of such a combination requires ECG monitoring especially at the beginning of treatment.

Combinations requiring safety precautions:

In common with other calcium antagonists, when diltiazem is used with drugs which may induce bradycardia or with antiarrhythmic drugs (e.g. amiodarone) or other antihypertensive drugs, the possibility of an additive effect should be borne in mind. Inhalation anaesthetics should be used with caution during diltiazem therapy. Tri/tetracyclic antidepressants and neuroleptics may increase the antihypertensive effects of diltiazem whilst the concomitant use of lithium with diltiazem may lead to neurotoxicity (extrapyramidal effects). Rifampin and other hepatic enzyme inducers may reduce the bioavailability of diltiazem and high doses of Vitamin D and/or high intake of calcium salts leading to elevated serum calcium levels may reduce the response to diltiazem.

Diltiazem is metabolised by CYP3A4 and could, by competitive inhibition of CYP3A4, affect the pharmacokinetics of other drugs metabolised by this enzyme. In addition inhibitors and inducers of CYP3A4 may affect the pharmacokinetics of diltiazem.

Diltiazem prolongs the sedative effect of medazolam and triazolam via metabolic interaction and decreases nifedipine clearance by 50%. Diltiazem may cause increases in the levels of digitoxin. Diltiazem has been shown to increase the bioavailability of imipramine by 30% probably due to inhibition of its first pass metabolism.

Diltiazem has been used safely in combination with diuretics, ACE-inhibitors and other anti-hypertensive agents. It is recommended that patients receiving these combinations should be regularly monitored. Concomitant use of diltiazem with alpha-blockers such as prazosin should be strictly monitored because of the possible synergistic hypotensive effect of the combination.

Case reports have suggested that blood levels of carbamazepine, cyclosporin, theophylline and phenytoin may be increased when given concurrently with diltiazem. Care should be exercised in patients taking these drugs. In common with other calcium antagonists diltiazem may cause small increases in plasma levels of digoxin. In patients taking H₂-antagonists concurrently with diltiazem there may be increased levels of diltiazem.

Magnification of the hypotensive and lipothymic effects (summation of vasodilator properties) of nitrate derivatives can occur. In patients on calcium inhibitors, prescriptions of nitrate derivatives should be made at progressively increasing doses. Diltiazem treatment has been continued without problem during anaesthesia, but diltiazem may potentiate the activity of curare-like and depolarising neuromuscular blocking agents, therefore the anaesthetist should be informed that the patient is receiving a calcium antagonist.

4.6 Pregnancy And Lactation

Pregnancy:

Diltiazem should not be taken during pregnancy. Women of child bearing-potential should exclude the possibility of pregnancy before commencing treatment by taking suitable contraceptive measures if necessary. In animal tests, Diltiazem was found to have a tetratogenic effects in some species of animal.

Diltiazem may suppress the contractility of the uterus. Definite evidence that this will prolong partus in full-term pregnancy is lacking. A risk of hypoxia in the foetus may arise in the event of hypotension in the mother and reduced perfusion of the uterus due to redistribution of blood flow due to peripheral vasodilatation. In animal experiments diltiazem has exhibited teratogenic effects in some animal species. In the absence of adequate evidence of safety in human pregnancy, VIAZEM XL should not be used in pregnancy or in women of childbearing potential.

Lactation:

Diltiazem is excreted in breast milk in concentrations similar to those in serum. If the use of diltiazem is considered essential, an alternative method of infant feeding should be instituted.

4.7 Effects On Ability To Drive And Use Machines

There are no studies on the effect of diltiazem when driving vehicles or operating machines. It should be taken into account that occasionally asthenia/fatigue and dizziness may occur. Treatment of hypertension with this medicinal product requires regular monitoring. Individual different reactions may affect the ability to drive. This risk should be considered especially at the beginning of treatment, when changing the drug, or in combination with alcohol.

4.8 Undesirable Effects

Certain undesirable effects may lead to suspension of treatment: sinus bradycardia, sino-atrial heart block, 2nd and 3rd degree atrioventricular heart block, skin rash, oedema of the lower limbs.

In hypertensive patients, adverse effects are generally mild and transient and are most commonly vasodilatory related events.

The following have been described in decreasing order of frequency: lower limb oedema, headache, hot flushes/flushing, asthenia/fatigue, palpitations, malaise, minor gastro-intestinal disorders (dyspepsia, abdominal pain, dry mouth, nausea, vomiting, diarrhoea, constipation) and skin rash. Erythema multiform and Stevens Johnson syndrome have been reported infrequently in patients receiving diltiazem hydrochloride. Vasodilatory related events (in particular, oedema) are dose-dependent and appear to be more frequent in elderly subjects.

Rare cases of symptomatic bradycardia and exceptionally sino-atrial block and atrioventricular block, hypotension, syncope, reduced left ventricular function have also been recorded. Isolated cases of hallucinations, depression, insomnia, hyperglycaemia and impotence have been reported.

Experience with use in other indications and with other formulations has shown that skin rashes are usually localised and are limited to cases of erythemia, urticaria or occasionally desquamative erthema, with or without fever, which regress when treatment is discontinued.

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

Dizziness, pruritis, nervousness, paraesthesia, articular/muscular pain, photo sensitisation, hypotension, gingival hyperplasia, and gynaecomastia, have also been observed.

4.9 Overdose

The clinical consequences of overdose can be severe hypotension leading to collapse, and sinus bradycardia which may be accompanied by isorhythmic dissociation and atrioventricular conduction disturbances. Observation in a coronary care unit is advisable. Vasopressors such as adrenaline may be indicated in patients exhibiting profound hypotension. Calcium gluconate may help reverse the effects of calcium entry blockade. Atropine administration and temporary cardiac pacing may be required to manage bradycardia and/or conduction disturbances.

Glucagon can be used in cases of established hypoglycaemia.

Diltiazem and its metabolites are very poorly dialysable.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Diltiazem is classified as a calcium channel blocker, benziothiazepine derivative, C08DB01, under the ATC classification. It selectively reduces calcium entry through voltage-dependent calcium-n channels into vascular smooth muscle cells and myocardial cells. This lowers the concentration of intracellular calcium which is available to activate contractile proteins. This action of diltiazem results in dilation of coronary arteries causing an increase in myocardial oxygen supply. It reduces cardiac work by moderating the heart rate and by reducing systemic vasculary resistance thus reducing oxygen demand. Diltiazem also prolongs AV conduction and has mild effects on contractility. Clinical data on morbidity and mortality are not available.

5.2 Pharmacokinetic Properties

Multiple dose pharmacokinetic studies have shown that the kinetics of VIAZEM XL are non-linear within the 120mg-360mg dosage range. Diltiazem is well absorbed, but has a highly saturable first pass effect leading to a variable absolute bioavailability, which is on average 35%. The saturable first pass effect results in higher than expected systemic exposure with increasing doses.

The protein binding is 80 to 85% and the volume of distribution is 5.0 l/kg.

Diltiazem is metabolised by CYP3A4 in the liver and 70% of the dose is excreted in urine, mainly as metabolites. The plasma levels of the two main metabolites, N-monodesmethyldiltiazem and desacetyldiltiazem, represent 35% and 15% of diltiazem levels respectively. The metabolites contribute around 50% of the clinical effect. Plasma clearance of diltiazem is approximately 0.5 l/h/kg. Plasma half-life of diltiazem is approximately 5-7 hours.

VIAZEM XL capsules allow a prolonged absorption of diltiazem and maximum levels are reached within 6 to 12 hours. Concomitant food intake with VIAZEM XL does not influence the pharmacokinetics of diltiazem. For most patients, chronic administration of VIAZEM XL 300mg once daily, results in therapeutic diltiazem levels (50-200ng/ml) over 24 hours. However, the inter-individual variability is high and individual dose adjustment based on therapeutic response is therefore necessary.

5.3 Preclinical Safety Data

Tests on reproductive functions in animals show that diltiazem decreases fertility in rats and that it is teratogenic in mice, rats and rabbits. Exposure during late pregnancy induces dystocia and a decrease in the number of live newborns in rats.

Detailed mutagenicity and carcinogenicity tests proved negative.

6. Pharmaceutical Particulars

6.1 List Of Excipients

- Sucrose Stearate

- Microcrystalline cellulose

- Povidone

- Magnesium Stearate

- Talc

- Titanium dioxide

- Hypromellose

- Polysorbate 80

- Polyacrylate dispersion 30% (dry)

- Simethicone emulsion

- Gelatine capsule

Gelatin capsule colours

Gelatin capsule markings (printed radially):

White printing ink contains:

Shellac, Ethyl Alcohol, Isopropyl Alcohol, n-Butyl, Propylene Glycol, Sodium Hydroxide, Polyvinylpyrrolidone, Titanium Dioxide

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Do not store above 25°C. Store in original package in a dry place away from any heat source, e.g. direct sunlight, heaters, steam, etc.

6.5 Nature And Contents Of Container

The capsules are packed in PVC/aluminium blisters. Pack sizes are 28 capsules per blister.

6.6 Special Precautions For Disposal And Other Handling

Swallow capsules whole, with a glass of water do not chew.

7. Marketing Authorisation Holder

Genus Pharmaceuticals Limited

T/A Genus Pharmaceuticals

Park View House

65 London Road

Newbury

Berkshire RG14 1JN

United Kingdom

8. Marketing Authorisation Number(S)

PL 06831/0232

9. Date Of First Authorisation/Renewal Of The Authorisation

10 June 2009

10. Date Of Revision Of The Text

25 August 2011