PepcidTwo

1. Name Of The Medicinal Product

Pepcidtwo chewable tablet

2. Qualitative And Quantitative Composition

Famotidine 10 mg

Magnesium hydroxide 165 mg

Calcium carbonate 800 mg

For excipients, see 6.1.

3. Pharmaceutical Form

Chewable tablet

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

4. Clinical Particulars

4.1 Therapeutic Indications

The short-term symptomatic relief of heartburn, indigestion, acid indigestion, and hyperacidity.

4.2 Posology And Method Of Administration

Adults and children 16 years of age or older:

One tablet to be chewed for the relief of symptoms. No more than two tablets to be taken in 24 hours.

Patients must seek medical advice if symptoms fail to respond, or if symptoms recur following self treatment with Pepcidtwo.

The maximum continuous treatment period is 6 days. The patient should not purchase a second pack of tablets without the advice of a pharmacist or doctor.

Elderly

No dosage adjustment is necessary.

Children less than 16 years of age

Not recommended.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

These tablets are not indicated in the following patient groups unless advised by their physician:

• Patients with moderate or severe renal failure (serum calcium should be monitored in such cases)

• Patients with severe hepatic impairment

• Patients suffering from any other illness or taking any medications either physician-prescribed or self-prescribed

• Patients who are middle aged or older with new or recently changed dyspeptic symptoms

• Patients with unintended weight loss in association with dyspeptic symptoms

4.4 Special Warnings And Precautions For Use

If patients have difficulty swallowing, or abdominal discomfort persists they should seek medical advice.

Gastric cancer and simple indigestion can have some symptoms in common. Therefore it is important that patients with symptoms such as weight loss, dysphagia, or anaemia, in addition to indigestion, should seek medical advice before starting any treatment, to avoid delay in investigation and diagnosis.

Patients who are taking non-steroidal anti-inflammatory drugs, especially the elderly, should consult their doctor before taking these tablets

As Pepcidtwo contains sucrose and lactose, it should not be taken by patients with fructose intolerance, glucose-galactose malabsorption syndrome, sucrase-isomaltase deficiency, lactase insufficiency or galactosaemia.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Famotidine

No drug interactions of clinical importance have been identified. Famotidine does not interact with the cytochrome P450-linked drug metabolising enzyme system. Famotidine does not affect blood alcohol levels following oral ingestion of ethanol.

Antacids

Antacids can decrease the absorption of some medicines. Concomitant administration of Pepcidtwo is therefore not indicated unless advised by a physician (see 4.3).

4.6 Pregnancy And Lactation

Pepcidtwo is not recommended for use in pregnancy. Before a decision is made to use the product during pregnancy, the physician should weigh the potential benefits against the possible risks involved.

Famotidine is secreted in human milk and magnesium salts may enter breast milk and cause diarrhoea in infants; therefore breast-feeding mothers should either stop breast-feeding or not take the product.

4.7 Effects On Ability To Drive And Use Machines

In clinical trials with Pepcidtwo, there has been no observed impairment of the ability to drive or operate machinery.

4.8 Undesirable Effects

Pepcidtwo has been shown to be generally well tolerated. In clinical trials the most common effects were headaches followed by nausea and diarrhoea. Other symptoms noted included abdominal distension, abdominal pain, dizziness, dry mouth, dyspepsia, eructation, flatulence, nervousness, paraesthesia, taste perversion and thirst.

Other side effects reported for famotidine alone, often when given at higher doses than Pepcidtwo, include anaphylaxis, angioedema, anorexia, arthralgia, cholestatic jaundice, constipation, fatigue, leucopenia, liver enzyme abnormalities, pancytopenia, pruritus, rash, urticaria, vomiting, and, in isolated cases, worsening of existing hepatic disease. Gynaecomastia has been reported rarely. In most cases that were followed up, it was reversible on discontinuing treatment.

Antacids containing calcium and magnesium salts can cause bloating, changes in stool frequency and consistency, and fullness.

4.9 Overdose

There is no experience to date with overdosage. The usual measures to remove unabsorbed material from the gastro-intestinal tract, clinical monitoring and supportive therapy should be employed.

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

5. Pharmacological Properties

H₂ ANTAGONIST/ANTACID.

(A02BA53: famotidine, combinations)

5.1 Pharmacodynamic Properties

Famotidine reduces the acid and pepsin production, as well as the volume of basal, nocturnal and stimulated gastric secretion. Magnesium hydroxide and calcium carbonate are antacids and neutralise intraluminal acid on contact. Pepcidtwo combines the prolonged duration of effect of famotidine with the rapid onset of action of antacids and has an acid neutralisation capacity of 21 mEq per tablet.

A study measuring gastric and oesophageal pH conducted on 23 patients demonstrated that the administration of Pepcidtwo with 60ml of water one hour after a high-fat evening meal produced an increase of oesophageal pH within 2 minutes. The increase of the gastric pH, above the increase observed with placebo and antacid alone, remained for 12 hours.

5.2 Pharmacokinetic Properties

The pharmacokinetic properties of famotidine are not significantly modified when administered with magnesium hydroxide and calcium carbonate as Pepcidtwo.

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.

Antacids

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 are 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.

5.3 Preclinical Safety Data

Extensive preclinical safety studies have been performed with famotidine in dogs, rats, mice and rabbits using oral and intravenous routes of administration. Minimal toxicological effects (after acute, subacute or chronic administration) have been observed, even at extremely high dosage levels and for extended periods of administration. No evidence of teratogenic, mutagenic or carcinogenic effects or alteration of reproductive function has been seen.

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.

6. Pharmaceutical Particulars

6.1 List Of Excipients

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)

Hydroxypropyl cellulose (E463)

Sodium lauryl sulphate

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).

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

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

3 years for blister packs (PVC/ACLAR)

6.4 Special Precautions For Storage

No special precautions for storage

6.5 Nature And Contents Of Container

Blister packs (PVC/ACLAR) or strip packs (Paper/PE/Aluminium/EAA) containing:

2, 4, 6, 8, 10 and 12 tablets.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire

SL6 3UG

United Kingdom

8. Marketing Authorisation Number(S)

PL 15513/0348

9. Date Of First Authorisation/Renewal Of The Authorisation

15 December 2008

10. Date Of Revision Of The Text

01 March 2011