McNeil Healthcare (Ireland) Ltd

Pepcidtwo Chewable Tablets

Famotidine 10mg

Magnesium Hydroxide 165mg

Calcium Carbonate 800mg

Each chewable tablet contains:

Famotidine 10.00 mg

Magnesium hydroxide 165.00 mg

Calcium carbonate 800.00 mg

For a full list of excipients, see section 6.1.

Chewable tablet.

Rose coloured, round, flat chewable tablet embossed with P.

Short-term symptomatic treatment of heartburn or acid regurgitations in adults and adolescents from 16 years old.

FOR ADULTS AND ADOLESCENTS (from 16 years old).

Chew one tablet thoroughly when symptoms occur, and swallow preferably with a glass of water. Do not exceed 2 tablets per day.

Treatment duration is limited to 2 weeks (see section 4.4 Precautions for use).

− Hypersensitivity to the active substances or any of the excipients,

− Severe renal failure.

Warnings:

* It is recommended to patients to seek medical advice in case of:

− symptoms associated with weight loss,

− difficulty swallowing or persistent abdominal discomfort,

− digestive troubles occurring for the first time or if these symptoms have recently changed,

− known hypercalcaemia, as this product contains calcium,

− known hypophosphataemia, as this product may worsen this condition,

− known hypercalciuria, or a history of renal calculi or nephrocalcinosis.

* In case of renal failure this product should only be taken under medical supervision and monitoring of serum magnesium and calcium should be undertaken.

* PEPCIDTWO should be used with caution in case of hepatic or renal impairment.

* As this product contains sucrose and lactose:

- patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

- patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

* With long term use, especially during concomitant treatment with other calcium products and/or Vitamin D products, there is a risk of hypercalcaemia with subsequent kidney function impairment.

Precautions for use:

If symptoms persist after 15 days of continuous treatment or get worse, an etiologic survey must be done and the conduct of the treatment should be re-evaluated.

Antacids interact with some other medicines taken orally.

Associations needing precautions for use :

A decrease of the absorption of some medicines administered concomitantly is observed.

As a precaution, it is recommended to take antacids separately from other medicines.

In general space out the doses more than 2 hours apart (see list below). However 4 hours should be left between administration of the product and administration of quinolones.

The absorption of certain NSAIDs, sulphonylurea antidiabetic agents and the oral anticoagulant dicoumarol can be enhanced by concomitant administration with the product.

+ Atenolol, metoprolol, propranolol, sotalol

+ Chloroquine

+ Tetracyclines

+ Diflunisal

+ Digoxin

+ Diphosphonate

+ Estramustine (due to the presence of calcium salts)

+ Fexofenadine

+ Iron (salts)

+ Sodium fluoride

+ Glucocorticoids (described for prednisolone and dexamethasone)

+ Indomethacin

+ Sodium polystyrene sulphonate resin

+ Ketoconazole

+ Lansoprazole

+ Phenothiazine neuroleptics

+ Penicillamine

+ Phosphorus (supplements)

+ Thyroxin

+ Gabapentin

+ Benzodiazépines

Associations to be taken into account :

+ Salicylates: Antacids increase the renal excretion of salicylates by alkalinization of the urine.

+ Probenecid inhibits the tubular secretion of famotidine and thereby increases the plasma concentrations of famotidine.

+ During concomitant use with cardiac glycosides, hypercalcaemia can increase the risk of digitalis toxicity (risk of dysrhythmia). Patients should be monitored with regard to ECG and calcium levels.

+ Thiazide diuretics may cause hypercalaemia due to decreased renal elimination of calcium. Since the product is only intended for short-term use there is no requirement to monitor calcium level in the plasma.

Pregnancy:

Data on a limited number of exposed pregnancies indicate no adverse effects of famotidine on pregnancy or on the health of the fetus/newborn child. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects of famotidine with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.

Data on a limited number of exposed pregnancies indicate no adverse effects of magnesium hydroxide or calcium carbonate on pregnancy or on the health of the fetus/newborn child. To date, no other relevant epidemiological data are available. Animal studies with magnesium hydroxide are insufficient. With calcium carbonate ossification abnormalities have been described after long-term treatment at high doses. The potential risk for humans is unknown.

Caution should be exercised when prescribing to pregnant women.

Lactation:

Famotidine is secreted via breast milk. There is a possibility of famotidine affecting the infant's gastric acid secretion. Magnesium salts may enter breast milk and cause diarrhoea in breast-fed infants. Therefore PEPCIDTWO should be avoided during breast-feeding.

Although it is not expected, if dizziness appears, patients must not drive or use machines.

The most common ADR's in clinical trials were headaches (1.3%), nausea (0.5%) and diarrhoea (0.4%).

Adverse Reactions By Body System Clinical Trials

Other side effects noted in isolated reports with higher dosages of famotidine in principle cannot be excluded.

There have been very rare reports of:

- Cutaneous: skin rashes, pruritus and urticaria, and, as with other H2 antagonists, severe skin reactions (toxic epidermal necrolysis).

- Hypersensitivity reactions: anaphylaxis, angioneurotic oedema, bronchospasm.

- Hepatic disorders including hepatic cholestasis and such as raised laboratory values for transaminases, gamma-GT, alkaline phosphatase and bilirubin.

- Neurological disorders such as hallucinations: disorientation, confusion and insomnia, epileptic seizures, drowsiness and agitation and depression related states. These have been reported to be reversible on stopping medication.

- Blood disorders such as thrombocytopenia, leucopenia, agranulocytosis and pancytopenia.

- Musculoskeletal disorders, such as muscle cramps.

- Others such as impotence, reduced libido, breast tension.

The following side effects are generally attributed to antacids containing calcium and magnesium salts: change in stool frequency and consistence, bloating and fullness.

Patients have tolerated doses up to 800 mg/day of famotidine for more than a year without development of significant adverse effects.

Pharmacotherapeutic group: H₂ ANTAGONIST/ANTACID.

(A02BA53: famotidine, combinations)

Famotidine reduces the acid and pepsin production, as well as the volume of basal, nocturnal and stimulated gastric secretion. Magnesium hydroxide and calcium carbonate have antacid properties by neutralisation mechanism.

Acid neutralisation capacity per tablet is evaluated at 21 mEq (USP method).

A study measuring gastric and oesophageal pH conducted on 23 patients demonstrated that the administration of the combination famotidine 10mg/antacid 21mEq with 60ml of water one hour after a high-fat evening meal produces an immediate increase of oesophageal pH.

The increase of the gastric pH, above the increase observed with placebo and antacid alone, remains for 12 hours.

The pharmacokinetic properties of famotidine are not significantly modified when administered with magnesium hydroxide 165mg and calcium carbonate 800mg.

Famotidine:

Famotidine obeys linear kinetics.

Famotidine is rapidly absorbed with dose-related peak plasma concentration occurring at 1-3 hours after administration.

The mean bioavailability of an oral dose is 40-45 %. It is not modified when taken during meals. First-pass metabolism is minimal. Repeated doses do not lead to accumulation of the drug.

Protein binding in the plasma is relatively low (15-20 %). The plasma half-life after a single oral dose or multiple repeated doses (for 5 days) is approximately 3 hours.

Metabolism occurs in the liver, with formation of an inactive metabolite, the sulfoxide.

Following oral administration, the mean urinary excretion of famotidine is 65-70 % of the absorbed dose, 25 to 30 % as unchanged compound. Renal clearance is 250 to 450ml/min, indicating some tubular excretion. A small amount may be excreted as the sulfoxide.

The half-life is prolonged in patients with renal impairment.

Calcium carbonate and magnesium hydroxide are converted to soluble chloride salts by gastric acid. Approximately 10% of the calcium and 15-20% of the magnesium is absorbed, and the remaining soluble chlorides are reconverted to insoluble salts, and are eliminated in the faeces. In individuals with normal kidney function the small amounts of calcium and magnesium that are absorbed are rapidly excreted by the kidneys.

Pre-clinical data for famotidine reveal no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.

Only limited toxicology data are available for magnesium hydroxide and calcium carbonate. These data indicate no special hazard for humans under normal conditions of use. Ossification abnormalities have been described in animals treated with calcium carbonate at high doses or long periods.

- Dextrates

- Confectioner's sugar (sucrose and maize starch)

- Lactose monohydrate

- Peppermint flavour (peppermint oil, modified food starch, maltodextrine, citric acid (E330), sodium ascorbate (E301), water)

- Cellulose acetate

- Magnesium stearate

- Hypromellose (E464)

- Hydroxypropylcellulose (E463)

- Sodium laurilsulphate

- Pregelatinised maize starch

- Cream flavour (sweet orange oils, ethanol, esters of acetic and butanoic acids, aliphatic alcohols and ketones, phenols, aliphatic and aromatic aldehydes, benzaldehyde, dextrin, maltodextrine, glucose, corn starch, calcium silicate, powdered vanilla extract, heliotropine, vanillin, silicone dioxide, water)

- Red ferric oxide (E172).

Not applicable.

2 years for strip packs (Paper/PE/Aluminium/EAA).

3 years for blister packs (PVC/ACLAR).

This medicinal product does not require any special storage conditions.

2 tablets in blister (PVC/ACLAR)

6 tablets in blister (PVC/ACLAR)

12 tablets in blister (PVC/ACLAR)

18 tablets in blister (PVC/ACLAR)

24 tablets in blister (PVC/ACLAR)

2 tablets in strip packaging (Paper/PE/Aluminium/EAA)

6 tablets in strip packaging (Paper/PE/Aluminium/EAA)

12 tablets in strip packaging (Paper/PE/Aluminium/EAA)

18 tablets in strip packaging (Paper/PE/Aluminium/EAA)

24 tablets in strip packaging (Paper/PE/Aluminium/EAA)

Not all pack sizes may be marketed.

No special requirements

McNeil Healthcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/58/1

Date of first authorisation: 29 September 2000

Date of last renewal: 21 September 2009

January 2011