INFORMATION FOR HEALTH PROFESSIONALS
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
APO-FAMOTIDINE 20mg tablets are beige, D-shaped (6.7 x 8.7mm), biconvex, film coated tablets identified APO over 20 on one side. Each tablet contains 20mg famotidine and typically weighs 215mg.
APO-FAMOTIDINE 40mg tablets are brown, D-shaped (6.7 x 8.7mm), biconvex, film coated tablets identified APO over 40 on one side. Each tablet contains 40mg famotidine and typically weighs 215mg.
Famotidine is a potent long acting histamine H2-receptor antagonist which competitively inhibits the action of histamine on the H2-receptors of the parietal cells. The primary clinically important pharmacologic activity is the inhibition of gastric juice secretion. Famotidine is effective in the treatment of duodenal ulcer, benign gastric ulcer, hypersecretory conditions and other conditions where the reduction of gastric secretion is desirable. Famotidine reduces the acid and pepsin content as well as the volume of basal, nocturnal and stimulated gastric secretion. In both normal volunteers and hypersecretors famotidine inhibited basal nocturnal and daytime gastric secretion as well as secretion stimulated by pentagastrin and food. After oral administration the onset of the antisecretory effect occurred within 1 hour. The maximum effect is dose dependent and occurs within 1 to 3 hours of dosing. Following oral doses of 20 mg and 40 mg in the evening, the mean nocturnal basal gastric acid secretion is inhibited by 86% and 94%, respectively, for up to 10 hours. When similar doses are given in the morning, the mean food-stimulated gastric acid secretion is suppressed by 76% and 84%, respectively, 3 to 5 hours after administration. After 8 to 10 hours post-dose, effectiveness is approximately 20 to 25% in the majority of patients. There was no cumulative effect with repeated doses. The nocturnal intragastric pH was raised by evening doses of famotidine 20 and 40mg to mean values of 5 and 6.4 respectively. When famotidine was given at breakfast the basal daytime interdigestive pH at 3-5 hours after dosing with 20 or 40mg was raised to about 5.
The presence of gastroesophageal reflux disease appears to correlate best with the percentage of time over 24 hours the oesophagus is exposed to acid. In patients with gastroesophageal reflux disease famotidine 20 and 40mg twice daily reduced intraoesophageal acid exposure into the normal range and were effective in healing oesophageal lesions. In patients treated for 6 months with famotidine 20mg twice daily the relapse of oesophageal erosions or ulceration was significantly less than in patients treated with placebo.
Famotidine is incompletely absorbed. The oral bioavailability of famotidine is about 40 to 45% and this is not altered to any clinically significant extent by the presence of food. Peak plasma levels occur in 1-3 hours with plasma levels after multiple doses being similar to those after single doses. Famotidine binds to plasma proteins to the extent of 15 to 20% of the absorbed dose. The apparent volume of distribution (Vd) is reported to range from 1.1 to 1.4 L/kg.
Famotidine undergoes minimal first-pass metabolism.
Famotidine has an elimination half-life (t1/2) of 2.5 to 3.5 hours, and is eliminated by renal (65-70%) and metabolic (30-35%) routes. The renal clearance ranges from 250 to 450 ml/min indicating active tubular excretion. The only metabolite identified in man is famotidine S-oxide.
Patients presenting impaired renal function may need the normal dosage adjusted. In patients with moderate or severe renal insufficiency (creatine clearance less than 10ml/min) the elimination half life of famotidine may be greater than 20 hours, and can reach 24 hours in anuric patients. Even though there is no evidence of side effects due to high plasma levels, Famotidine dosage can be reduced or dosage intervals lengthened to avoid the possibility of excess accumulation of the medicine.
Famotidine is indicated for the treatment of:
Duodenal ulcer
Prevention of relapses of duodenal ulceration
Benign gastric ulcer
Prevention of relapses of benign gastric ulcer
Hypersecretory conditions such as Zollinger-Ellison syndrome
Symptomatic relief of gastroesophagel reflux disease
Healing of oesophageal erosion or ulceration associated with gastroesophageal
reflux disease
Prevention of relapses of symptoms and erosions or ulcerations associated with
GERD
Antacids may be given concomitantly with these medicines if needed for further pain relief.
Duodenal Ulcer:
For acute therapy, the recommended dose is 40mg once daily at bedtime for 4
to 8 weeks. Reduction of nocturnal gastric acid secretion appears to be the most
important factor in healing duodenal ulcers. Alternatively, 20mg twice daily may
be administered. Healing will occur in most cases of duodenal ulcer within 4
weeks depending on the patients clinical response. If the ulcers have not healed
completely after 4 weeks then treatment should be continued for a further 4 week
period.
Maintenance therapy may be necessary to protect against relapse of duodenal
ulcer in patients with a tendency of recurrence or complications. The initial
therapy may be continued at a reduced dosage of 20mg once daily at bedtime for
up to 6 to 12 months in such circumstances.
Benign gastric ulcer:
The recommended dose is 40mg once daily taken at night. Alternatively, 20mg
twice daily may be administered. Most patients demonstrate healing of gastric
ulcers within 8 weeks but therapy may be shortened if endoscopy reveals earlier
healing of the ulcer.
Maintenance therapy may be necessary to protect against the recurrence of benign
gastric ulcer. The recommended dose is one 20mg tablet, taken at night which may
be given for up to one year.
Gastroesophageal Reflux Disease:
For mild to moderate disease, the recommended dosage is 20mg twice daily. For
erosive oesophagitis associated with gastroesophageal reflux disease, the
recommended dosage is 40mg twice daily.
Maintenance therapy may be necessary for the prevention of recurrence of
symptoms and erosions or ulcerations associated with gastroesophageal reflux
disease the recommended daily dose is 20mg of Famotidine twice daily.
Zollinger-Ellison Syndrome and other hypersecretory conditions:
Doses need to be individualised but the usual oral starting dose is 20mg every 6 hours, although some patients may need higher initial doses. Doses of up to 800mg per day have been administered to some patients with severe Zollinger-Ellison syndrome. If a patient has been receiving another H2 antagonist and are changed to APO-FAMOTIDINE a higher starting dose than that recommended for new cases is advised. The starting dose will depend upon the severity of the case and the last dose of H2 antagonist previously taken. Therapy should be continued for as long as clinically indicated.
For patients presenting severe dysfunction i.e. creatinine clearance of less than 10mL/min, or moderate dysfunction i.e. creatinine clearance of <50ml/min the elimination half life of APO-FAMOTIDINE is increased. In patients with severe renal insufficiency the elimination half life may exceed 20 hours, reaching approximately 24 hours in anuric patients. As CNS adverse events have been reported in patients with moderate and severe renal insufficiency, the dose of APO-FAMOTIDINE may be reduced to half the dose or the dosing interval may be prolonged to 36-48 hours, as indicated by the patients clinical response. This is to avoid excess accumulation of the drug.
Dosage adjustments are not necessary for geriatric patients unless there is a decrease in renal function, where the clearance of the drug may be reduced.
Safety and effectiveness of APO-FAMOTIDINE have not been established.
Hypersensitivity to any component of the medication.
Cross sensitivity in this class of compounds has been observed. APO-FAMOTIDINE should not be administered to patients with a history of hypersensitivity to other H2 receptor antagonists.
Gastric malignancy should be excluded before therapy with famotidine is commenced.
Caution is required in patients with moderate and severe renal insufficiency as CNS adverse events have been reported. Longer intervals between doses or lower doses may need to be used in patients with moderate (creatinine clearance <50ml/min) or severe (creatinine clearance <10mL/min) renal insufficiency to adjust for the longer elimination Half-life of famotidine. (see Dosage and Administration).
Minimal toxicologic effects have been observed in studies with famotidine even at extremely high dosage levels and for prolonged periods of administration. Reproductive studies performed in rats and rabbits at doses approximately 2500 and 625 times the maximum recommended human dose have revealed no evidence of impaired fertility or foetal harm due to famotidine. Studies have revealed no evidence of mutagenic or carcinogenic effects.
Category B1
Although animal studies have not indicated any incidence of teratogenicity, famotidine should be avoided in pregnancy unless in the opinion of a medical practitioner, the benefits outweigh the potential risk to the foetus.
Famotidine is detectable in human milk. Nursing mothers should either discontinue this medication or discontinue nursing.
Famotidine is generally well tolerated. Headache, dizziness, constipation or diarrhoea are the most common side-effects but are generally of mild to moderate severity.
Other effects which have been reported in less than 1% of people taking famotidine include nausea, vomiting, rash, pruritus and urticaria, liver enzyme abnormalities, cholestatic jaundice, artgralgia, weakness, arthralgia, fatigue, abdominal discomfort or distention, dry mouth, anorexia, muscle cramps and heartburn. Reversible psychic disturbances including depression, anxiety disorders, agitation, confusion and hallucinations have also been reported.
Hypersensitivity reactions such as anaphylaxis, bronchospasm and angioedema have been rarely reported. Toxic epidermal necrolusis has been reported very rarely with H2 receptor antagonists.
Increases in serum transaminases (AST, ALT), alkaline phosphatase (ALP) and creatine may occur and occasionally require discontinuation of the drug.
The following side effects have been reported but a causal relationship to famotidine therapy has not been established: Decreased libido, insomnia, paresthesia, disorientation, grand mal seizure, leukopaenia, somnolence, agranulocytosis, pancytopenia and thrombocytopenia. There have been rare cases of impotence and gynecomastia reported, but the incidence of these has been no greater than that seen with the placebo.
Famotidine does not interact with cytochrome P-450 (microsomal) enzyme systems to any clinically significant degree. The hepatic metabolism of medicines such as theophylline, diazepam, propanolol, aminopyrine, antipyrine, warfarin, phenytoin, and procainamide appear unaffected. Indocyanine green as an index of hepatic blood flow and/or hepatic medicine extraction has been tested but no significant effects were found.
There have been no drug interactions reported to date.
In addition, studies with famotidine have shown no augmentation of expected blood alcohol levels resulting from alcohol ingestion.
Famotidine appears to be well tolerated even after large doses. Patients presenting Zollinger-Ellison syndrome have taken doses of 800mg daily for one year without any significant side effects.
However, in the case of an overdosage the usual methods of gastric lavage and/or supportive therapy should be instituted.
Store below 30°C.
Protect from heat, light and moisture.
Prescription Only Medicine - for 20mg tablets, bottle packs of 100 and blister packs of 60, and 40mg tablets, bottle packs of 100 and blister packs of 30.
Pharmacy Only Medicine - for 20mg tablets, blister packs of 10 and 20.
APO-FAMOTIDINE 20mg tablets:
Bottles of 100 tablets.
Blister packs of 10, 20 and 60 tablets.
APO-FAMOTIDINE 40mg tablets:
Bottles of 100 tablets.
Blister packs of 30 tablets.
Tablets contain lactose and red and yellow ferric oxides as the colouring agents.
APOTEX NZ LTD
32 Hillside Road
Glenfield, Auckland
Private Bag 102995
North Shore Mail Centre
Tel: (09) 444 2073
Fax: (09) 444 2951
21 August 2001