SECADINE Tablets 200 mg (film-coated tablets); SECADINE Tablets 400 mg (film-coated tablets); SECADINE Syrup

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

SECADINE Tablets 200 mg (film-coated tablets)
SECADINE Tablets 400 mg (film-coated tablets)
SECADINE Syrup

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

SECADINE Tablets 200 mg (film-coated tablets)
SECADINE Tablets 400 mg (film-coated tablets)
SECADINE Syrup

COMPOSITION:
SECADINE Tablets 200 mg : Each tablet contains 200 mg cimetidine
SECADINE Tablets 400 mg : Each tablet contains 400 mg cimetidine

SECADINE Syrup

: Each 5 mL syrup contains 200 mg cimetidine as the hydrochloride
Preserved with methyl p-hydroxybenzoate 0,10% m/v and propyl p-hydroxybenzoate 0,02% m/v
Contains ethyl alcohol 2,9% v/v

PHARMACOLOGICAL CLASSIFICATION:
A 11.4.3 Antacids: Other

PHARMACOLOGICAL ACTION:
SECADINE inhibits both the stimulated and basal secretion of gastric acid and reduces pepsin output. It competitively inhibits the action of histamine at the histamine H2-receptor and is thus a histamine H2- receptor antagonist.
Studies have shown the degree of inhibition of basal acid secretion to vary between 80 and 100% and of stimulated acid secretion between 56 and 98% with a duration of up to 5 hours, depending on the dosage and the type of stimulation.

Pharmacokinetics:
SECADINE is rapidly absorbed after oral administration. The half-life of SECADINE is approximately 2 hours. The principal route of excretion is the urine.

INDICATIONS:
SECADINE is indicated in:

1.	The treatment of duodenal and benign gastric ulceration and peptic oesophagitis; recurrent ulceration; stomal ulceration and other conditions where reduction of gastric acid secretion has been shown to be beneficial.
2.	In patients with a history of recurrent duodenal ulceration relapse after healing is prevented during treatment at reduced dosage for up to 1 year.
3.	Management of pathological hypersecretion (such as Zollinger-Ellison Syndrome, systemic mastocytosis, multiple endocrine adenomas).
4.	SECADINE is indicated in the management of those patients who are of high risk from haemorrhage of the upper gastro-intestinal tract due to hepatic failure.

CONTRA-INDICATIONS:
SECADINE is contra-indicated in any patients who are known to have hypersensitivity to the drug.

DOSAGE AND DIRECTIONS FOR USE:
Adults:

1.	Active Ulcer: In active duodenal, benign gastric and stomal ulceration: The usual dose is 200 mg three times a day with meals and 400 mg at bedtime. 400 mg twice a day, with breakfast and at bedtime has also been shown to be effective. The preferred dose is 200 mg three times a day with meals and 400 mg at bedtime. If there is inadequate symptomatic improvement or other evidence of continuing ulceration, this dose may be increased to 400 mg four times a day, taken with meals, and at bedtime. Treatment should be continued for at least four weeks, even if symptomatic relief has been achieved in a shorter time. In duodenal ulcer: the efficacy of a single bedtime dose of 800 mg has been shown to be comparable to that of a daily dose of 800 mg divided in two administrations (400 mg in the morning and 400 mg at bedtime).
2.	Maintenance Treatment: Prophylaxis of Recurrent Ulcer: In patients with a history of recurrent duodenal ulceration, relapse after healing is prevented during treatment at reduced dosage for a period of up to 1 year. It is recommended, after healing, to continue treatment of reduced dosage for as long as the physician deems necessary to prevent a relapse. A maintenance dose of 400 mg at bedtime has been shown to confer protection against recurrence after duodenal ulceration, during this period of 1 year while on maintenance treatment; some patients may require 400 mg twice a day.
3.	In Peptic Oesophagitis: 400 mg four times a day, taken with meals and at bedtime for up to 12 weeks, is recommended. 0,8 to 1,6 g/day, depending on the degree of severity of the condition, may be used. A single bedtime dose of 800 mg may be effective in patients with peptic oesophagitis. 400 mg twice daily in the morning and at bedtime has also been shown to be effective. Severe cases may require up to 1,6g/day given in divided doses.
4.	In Zollinger-Ellison syndrome and other cases of high gastric secretion: The usual dose is 200 mg three times a day with meals and 400 mg at bedtime, but it may be necessary to increase the dose to 400 mg four times a day. In some patients it may be necessary to administer SECADINE more frequently. Doses should be adjusted to individual needs and should continue as long as clinically indicated.
5.	In the management of those patients who are of high risk from haemorrhage of the upper gastrointestinal tract due to hepatic failure and treatment with immuo-suppressive agents, following kidney transplant: Patients with hepatic failure who are at high risk from haemorrhage can be treated with normal doses of SECADINE. The usual dose is 200 mg three times a day with meals, and 400 mg at bedtime. It may be necessary to increase the dose to 400 mg four times a day. For the dosage for patients following kidney transplant, please refer to "Side-effects and special precautions".

Since SECADINE may not always give immediate symptomatic relief, antacids should be made available to patients as needed for relief of pain.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Diarrhoea, tiredness, dizziness, rash and sometimes severe and reversible alopecia have been reported in patients during treatment with SECADINE.
Gynaecomastia has been reported. The condition remained unchanged or returned toward normal with continuing SECADINE treatment. Reversible impotence has been reported in rare instances.
Decreased white cell counts in H2-antagonist treated patients in including agranulocytosis have been reported including reports of occurrence on rechallenge.
Cases of thrombocytopenia, pancytopenia and aplastic anaemia have also been reported. Cases of reversible confusional states, slurred speech, hallucinations, delirium and coma, have been reported, usually in children, elderly and/or severely ill patients, such as those with renal insufficiency or organic brain syndrome.
Increases in plasma creatinine hove been reported. These did not progress with continued therapy and disappeared of the end of therapy. Some increases in serum transaminase and cases of hepatitis, fever and interstitial nephritis and pancreatitis, which cleared on withdrawal of the drug, have been reported.
SECADINE has been administered to patients with impaired renal function. A transient rise in serum ureum and serum creatinine concentration were found in patients with moderate renal failure.
In patients with impaired renal function, dosage should be reduced according to creatinine clearance. The following dosages are suggested: Creatinine clearance of 0 to 15 mL per minute, 200 mg twice a day; 15 to 30 mL per minute, 200 mg three times a day; 30 to 50 mL per minute, 200 mg four times a day; over 50 mL per minute, normal dose.
Circulating cimetidine levels are reduced by haemodialysis. Therefore, the drug should be administered at the end of dialysis.
Rare occurrences of anaphylaxis have been reported in patients treated with H2-antagonists.
The possibility of malignancy in gastric ulcer should be excluded since the symptoms may respond to SECADINE treatment.
On current evidence it is recommended that no anticholinergic agents should be administered concurrently with cimetidine for maintenance treatment because of the possibility of drug interaction.

In view of a report that glucose handling was impaired after long term cimetidine administration, caution should be observed in the treatment of diabetics or elderly patients with cimetidine.

Drug interaction:
SECADINE apparently through on effect on certain microsomal enzyme systems has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, chlordiazepoxide, diazepam, nifedipine and theophylline; thereby delaying elimination and increasing blood levels of these drugs. Since clinically significant effects have been reported with the warfarin anticoagulants, dose monitoring of prothrombin time is recommended, and adjustment of the anticoagulant dose may be necessary when SECADINE is administered concomitantly. Interaction with phenytoin, theophylline and calcium channel blockers, has also been reported to produce adverse clinical effects. Increased plasma levels of nifedipine have been reported during concomitant cimetidine administration. For concomitant administration of these two drugs, cautious titration of nifedipine is advised.
Doses of the drugs mentioned above and other similarly metabolized drugs, may require adjustments when starting or stopping concomitantly administered SECADINE, to maintain safe, optimum therapeutic blood levels.

Use in pregnancy and lactation:
The safely of SECADINE in pregnancy has not yet been established. SECADINE should not be administered to pregnant and lactating patients.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Acute overdosage of up to 100 tablets (20 grams) has been reported several times with no significant ill effects. Induction of vomiting and/or gastric lavage may be employed together with symptomatic and supportive therapy.

IDENTIFICATION:

SECADINE Tablets 200 mg	:	Pale green, film coated tablets
SECADINE Tablets 400 mg	:	Pale green, oblong shaped, film coated with convex faces and flat sides.
SECADINE Syrup	:	Clear, orange coloured peach flavoured syrup.

PRESENTATION:

SECADINE Tablets 200 mg	:	Securitainers of 150 and 60 tablets.
SECADINE tablets 400 mg	:	Securitainers of 60 tablets.
SECADINE Syrup	:	Bottles containing 200 mL.

STORAGE INSTRUCTIONS:
Store below 25°C.
Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:

SECADINE Tablets 200 mg	:	27/11.4.3/0102
SECADINE Tablets 400 mg	:	27/11.4.3/0103
SECADINE Syrup	:	27/11.4.3/0104

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
XIXIA Pharmaceuticals (Pty) Ltd
15 Thora Crescent
Wynberg Ext. 3
Sandton
P.O. Box 2080, Gallo Manor, 2052

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

4 May 1993.

P1309