PRO PLUS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Pro Plus

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Caffeine Anhydrous EP 50.0mg

3 PHARMACEUTICAL FORM

Tablet

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the relief of temporary tiredness.

4.2 Posology and method of administration

Taken orally

Adults         Take 1–2 tablets with water if preferred, as required during the day.

Do not exceed 2 tablets in any three hour period or 8 tablets a day.

Elderly Take 1–2 tablets with water if preferred, as required during the day. persons:       Do not exceed 2 tablets in any three hour period or 8 tablets a day.

Children:      Pro-Plus should not be taken by children under 16 years.

As caffeine is found naturally in tea, coffee and chocolate, and in some carbonated drinks there is the potential for users to take more than the recommended 400mg/day of caffeine (8 tablets) per day. Therefore users should take account of dietary sources of caffeine and ensure that they do not exceed the stated dose.

Typical amounts of caffeine available from dietary sources are

Brewed coffee; 50–100mg/100ml*

Instant coffee and tea: 20–73mg/100ml*

Carbonated drinks (cola) 9–19mg/100ml*

Chocolate 5–20mg/100ml

(*100ml is equivalent to about 1 small cup of fluid)

4.3 Contraindications

Hypersensitivity to caffeine or any of the ingredients

Pro Plus should not be used by people who have been diagnosed with hypertension or who are receiving antihypertensive medication, or who have a history of cardiac arrhythmia.

Pro Plus should not be used by patients recovering from chronic alcoholism who are taking disulfiram.

Pro Plus should not be used if antidepressants (including lithium carbonate), anxiolytics (including clozapine) and sedatives are being used , or by persons with anxiety disorders.

Pro Plus should not be used by any persons who are also taking ephedrine (see also section 4.5).

As Pro Plus contains sorbitol it should not be taken by persons with rare hereditary problems of fructose intolerance.

Caffeine shares the same metabolic pathway as theophylline and therefore Pro Plus should not be used concurrently with theophylline.

Pro Plus should not be taken during pregnancy and lactation (See also 4.6 below).

4.4 Special warnings and precautions for use

Caffeine naïve and caffeine sensitive individuals may be more prone to the undesirable effects of caffeine (See section 4.8).

4.5 Interaction with other medicinal products and other forms of interaction As caffeine is found naturally in tea, coffee and chocolate, and in some carbonated drinks there is the potential for users to take more than the recommended 400mg/day of caffeine (8 tablets) per day. Therefore users should take account of dietary sources of caffeine and ensure that they do not exceed the stated dose (See section 4.2)

Xanthine derivatives such as caffeine can weaken the vasodilating effect of substances used for myocardial imaging such as adenosine and dipyridamole.

Therefore, caffeine should be avoided for 24 hours before myocardial imaging.

Caffeine, a CNS stimulant, has an antagonistic effect towards the action of sedatives and tranquilizers.

Caffeine may enhance the tachycardic effect of phenylpropano­lamine. Caffeine exerts a competitive inhibition of the metabolism of clozapine.

Therefore clozapine and caffeine must not be used concurrently (see contraindications).

Caffeine can increase blood pressure and counters the hypotensive action of Beta blockers such as Atenolol, Metoprolol, Oxprenolol and Propranolol. Pro Plus should not be used at the same time as beta blockers.

As caffeine is a CNS stimulant is counteracts the effects of sedatives.

Disulfiram increases caffeine clearance by up to 50%. Concomitant use of disulfiram and caffeine should be avoided (see contraindications).

Use of lithium carbonate and caffeine may cause a small to moderate rise in serum lithium levels. Concomitant use should be avoided (see contraindications).

Monoamine oxidase inhibitors may increase the stimulant effects of caffeine.

Methoxsalen reduces clearance of caffeine and may increase the effects of caffeine.

Phenytoin doubles caffeine clearance, although caffeine does not affect the metabolism of phenytoin.

Pipemidic acid reduces caffeine clearance, enhancing the effects of caffeine. Theophylline and caffeine share the same metabolic pathway, leading to increased clearance times for theophylline when used concurrently with caffeine. Concomitant use should be avoided (see contraindications).

Levothyroxin, like caffeine can increase blood pressure, and therefore these two active ingredients should not be used concurrently.

Ephedrine and caffeine interact to produce significant cardiovascular effects. Therefore caffeine should be avoided when ephedrine is being taken.

4.6 Fertility, Pregnancy and lactation

For Pro Plus no clinical data on exposed pregnancies are available.

Animal studies do not indicate any direct or indirect harmful effects with respect pregnancy, embryonic/foetal development, parturition or postnatal development.

Epidemiological studies have suggested that use of caffeine during pregnancy has been implicated with low birth weight, spontaneous abortion and preterm delivery. Based on these reviews, the recommended maximum daily intake of caffeine suggested is not more than 300mg of caffeine or 6 Pro Plus tablets. Given that caffeine is available from other dietary sources (coffee, tea, carbonated drinks etc), the use of Pro Plus is not recommended during pregnancy.

As caffeine is secreted into breast milk and caffeine half life is prolonged in infants up to the age of 6 months, Pro Plus should not be taken by mothers who are breast feeding.

4.7 Effects on ability to drive and use machines

At recommended doses Pro Plus is unlikely to have any adverse effects with respect to driving or operating machinery.

4.8 Undesirable effects

At doses up to 400 mg per day undesirable effects are not normally observed in healthy individuals. However some users who are caffeine naive, have abstained from caffeine for a period, or who are more sensitive to caffeine, may experience effects more commonly seen at higher doses. These include tremor, insomnia, nervousness, irritability, anxiety, headache, tinnitus, arrhythmia and tachycardia, diuresis, gastrointestinal disturbances and elevated respiration. Individuals who experience these effects must stop taking Pro Plus and any other dietary caffeine.

Following regular use of caffeine, cessation of intake may lead to withdrawal symptoms which may last up to a week and which include headache, tiredness and decreased alertness.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Symptoms:

Pallor

Dilated pupils

CNS effects comprising insomnia and restlessness, rigidity, tonic posturing and convulsions, nervousness, irritability, headache, excitement, restlessness, rapid speech,

Cardiovascular effects such as tachycardia, and cardiac arrhythmias and systemic hypertension

Diuresis and emesis effects leading to electrolyte imbalances

Tinnitus

Gastrointestinal disturbances including vomiting and abdominal cramps

Elevated respiration

Treatment

Treatment consists of withdrawal of caffeine followed by close monitoring of plasma levels of caffeine and electrolytes

Caffeine plasma level of 1mg/ml should be considered toxic.

The benefit of gastric contamination is uncertain.

Consider activated charcoal (50g for adult;10–15g for children) only if the patient presents within 1 hour of ingestion of a potentially toxic amount.

Gastric lavage may be employed in adults (within 1 hour of a potentially lifethreatening overdose), and restoration of electrolyte balance as necessary. Haemoperfusion has also been used successfully to treat caffeine overdose.

Monitor pulse , BP and cardiac rhythm. Supportive cardiovascular measures should be used as required.

Consider 12 lead ECG and measure U &Es. Correct hypokalaemia cautiously. Tachycardia with adequate cardiac output is best left untreated.

Ventricular arrhythmias occurring in a patient who is having convulsions are best treated with amiodarone or disopyramide rather than lignocaine or mexiletine since the latter may exacerbate convulsions.

If the systolic BP>220 and diastolic>140mmHg in the absence of long-standing hypertension give diazepam.

Persistent hypertension may respond to a beta-blocker. If hypertension is unresponsive to above measures, discuss with your local poisons service. If agitated, sedate with oral diazepam. Alternatively, give oral or parenteral haloperidol for adults. Beta blockers such as metoprolol or esmolol should be used in extreme cases (care in asthmatics).

Control convulsion with intravenous diazepam or lorazepam. Correct acid base and metabolic disturbances. Phenytoin may be useful if fits are unresponsive to above measures.

Other measures as indicated by the patient’s clinical condition.

5.1 Pharmacodynamic properties

Caffeine is a methylxanthine which, like theophylline, inhibits the enzyme phosphodiesterase and has an antagonistic effect on central adenosine receptors. It is a stimulant to the CNS, particularly the higher centres, and it can produce a condition of wakefulness and increased mental activity. It may also stimulate the respiratory centre, increasing the rate and depth of respiration. Its bronchodilating properties are weaker than those of theophylline. Caffeine facilitates the performance of muscular work and increases the total work which can be performed by a muscle. The diuretic effect of caffeine is weaker than that of theophylline.

5.2 Pharmacokinetic properties

Caffeine passes readily into the central system and into the saliva. There is however, little evidence of accumulation in any particular tissue. Caffeine is absorbed readily after oral administration but absorption from the gastrointestinal tract may be erratic.

It is metabolised almost completely and is excreted in the urine as: 1-methyluric acid, and l-methylxanthine, and other metabolites.

5.3 Preclinical safety data

Not applicable.

6.1

6.2

Sorbitol, Magnesium Stearate.

Not applicable.

6.3

36 Months.

6.4 Special precautions for storage None.

6.5 Nature and contents of container

Tablets strip-packed in groups of 2 or 6, using 25 mu soft temper aluminium foil extrusion-coated 35gsm polythene. A strip of tablets is packaged in a catch cover; or packaged in printed cartons. (2, 4, 6, 8, 12, 16, 24, 36, 48, 56, 96 tablets).

Blister packs comprising of 250um PVC coated with 40gsm PVDC which is sealed to 20um hard tempered aluminium foil. (2, 4, 6, 8, 12, 16, 24, 36, 48, 56, 96 tablets).

Alternatively, 100 tablets are packed directly into a white plastic tube 87mm tall by 27mm diameter, printed red on white, with a 25mm plastic foam wad and a blue 25mm stopper. The tube is packed in a printed carton.

6.6 Special precautions for disposal

No special precautions necessary.

7 MARKETING AUTHORISATION HOLDER

G R Lane Health Products Ltd.

Sisson Road

Gloucester

GL2 OGR

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 01074/0253