Spastone Rm

Uses

Dicycloverine is used for:

• Functional bowel/ irritable bowel syndrome
• Urinary incontinence secondary to unstable detrusor muscle
• Infantile colic
• GIT spasm
• Colicky abdominal pain
• Diverticulitis
• Abdominal colic

Mefenamic acid is used in mild to moderate pain including headache, dental pain, postoperative and postpartum pain, dysmenorrhoea, menorrhagia, in musculoskeletal and joint disorders such as osteoarthritis and rheumatoid arthritis; and in children with fever and juvenile idiopathic arthritis.

Ranitidine is used for:

• Treatment of active duodenal ulcer
• Benign gastric ulcer
• Treatment & prevention of ulcer associated with non-steroidal anti-inflammatory agent
• Post operative stress ulcer.
• Zollinger-Ellison Syndrome.
• Gastroesophageal reflux disease (GERD).
• Gastro-intestinal haemorrhage from stress ulcer in seriously ill patient.
• Recurrent haemorrhage in patients with bleeding peptic ulcer.
• Before general anesthesia in patient considered to be at risk of acid aspiration particulary obstetric patients.

Spastone Rm is also used to associated treatment for these conditions: Functional bowel syndrome, Irritable Bowel Syndrome (IBS), Gastrointestinal cramps caused by GasMild pain, Primary Dysmenorrhoea, Gastrointestinal cramps, Moderate PainAcid Aspiration Syndrome, Ankylosing Spondylitis (AS), Duodenal Ulcer, Erosive Esophagitis, Gastric Ulcer, Gastric hypersecretion, Gastro-esophageal Reflux Disease (GERD), Healing, Heartburn, Osteoarthritis (OA), Peptic Ulcer Disease, Rheumatoid Arthritis, Stress Ulcers, Zollinger-Ellison Syndrome, Active duodenal ulcers, Benign gastric ulcer healing, Benign gastric ulcers, Duodenal ulcer healing, Post-operative peptic ulcer, Recurrent hemorrhage from bleeding ulcers

How Spastone Rm works

Dicyclomine achieves its action partially through direct antimuscarinic activity of the M1, M3, and M2 receptors; and partially through antagonism of bradykinin and histamine. Dicyclomine non-competitively inhibits the action of bradykinin and histamine, resulting in direct action on the smooth muscle, and decreased strength of contractions seen in spasms of the ileum.

Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.

After a meal, the hormone gastrin, produced by cells in the lining of the stomach, stimulates the release of histamine, which then binds to histamine H2 receptors, leading to the secretion of gastric acid. Ranitidine reduces the secretion of gastric acid by reversible binding to histamine (H2) receptors, which are found on gastric parietal cells. This process leads to the inhibition of histamine binding to this receptor, causing the reduction of gastric acid secretion. The relief of gastric-acid related symptoms can occur as soon as 60 minutes after administration of a single dose, and the effects can last from 4-10 hours, providing fast and effective symptomatic relief.

Dosage

Spastone Rm dosage

Oral dosage forms-

• Adults:10 to 20 mg three times a day.
• Children >6 months of age: 5 to 10 mg three times a day.
• Children <6 months of age: Dose must be determined by the doctor.

Oral dicycloverine Hydrochloride should be started as soon as possible

Intramuscular dosage form

• Adults:Intramuscular injection. Not for intravenous use. The recommended intramuscular dose is 80 mg daily (in 4 equally divided doses).

Intramuscular dosage form should not be used for periods longer than 1 or 2 days.

As with other NSAIDs, the lowest dose should be sought for each patient. Therefore, after observing the response to initial therapy with Mefenamic acid, the dose and frequency should be adjusted to suit an individual patient's needs.Administration is by the oral route, preferably with food.

• Adult: A 500 mg dose should be given to adults up to three times (1.5 g total) per day.
• Infants over 6 months: 25 mg/kg of body weight daily in divided doses for not longer than 7 days.

Ranitidine Tablet & Syrup:

Duodenal and gastric ulcer: The usual dosage is 150 mg twice daily taken in the morning and evening or 300 mg as a single daily dose at night for 4 to 8 weeks.

Reflux oesophagitis: 150 mg twice daily or 300 mg at bed time for up to 8 weeks.

Zollinger Ellison syndrome: 150 mg 3 times daily and increased if necessary up to 6 g daily in divided doses. Dosage should be continued as long as clinically indicated.

Episodic dyspepsia: 150 mg twice daily or 300 mg at bed time for up to 6 weeks.

Maintenance: 150 mg at night for preventing recurrences.

Child (peptic ulcer)

Ranitidine IV injection & IV Infusion:

Ranitidine injection may be given either as a slow (over a period of at least two minutes) intravenous injection of 50 mg, after dilution to a volume of 20 ml per 50 mg dose, which may be repeated every six to eight hours; or as an intermittent intravenous infusion at a rate of 25 mg per hour for two hours; the infusion may be repeated at six to eight hour intervals; or as an intramuscular injection of 50 mg (2 ml) every six to eight hours. In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or the prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, parenteral administration may be continued until oral feeding commences.: 2-4 mg/kg twice daily, maximum 300 mg daily.

In the prophylaxis of upper gastrointestinal haemorrhage from stress ulceration in seriously ill patient sapriming dose of 50 mg as low as intravenous injection followed by a continuous intravenous infusion of 0.125-0.250 mg/kg/hour may be preferred. In patients considered to be at risk of developing aspiration syndrome Ranitidine injection 50 mg may be given intramuscularly or by slow intravenous injection 45 to 60 minutes before induction of general anaesthesia.

Children: The recommended oral dose for the treatment of peptic ulcer in children is 2 mg/kg to 4 mg/kg twice daily to a maximum of 300 mg ranitidine per day. Safety and effectiveness of Ranitidine injection have not been established in case of children.

Reconstitutions

Slow IV inj: Ranitidine 50 mg diluted to a concentration ≤2.5 mg/mL (e.g. total of 20 mL) with NaCl 0.9% inj or dextrose 5% or 10%, lactated Ringer's, Na bicarbonate 5% soln.

Intermittent slow IV infusion: Ranitidine 50 mg diluted to a concentration ≤0.5 mg/mL (e.g. total of 100 mL) of dextrose 5% inj or NaCl 0.9%, lactated Ringer's, Na bicarbonate 5% soln.

Continuous IV infusion: Ranitidine 150 mg diluted in 250 mL of dextrose 5% inj or NaCl 0.9%, lactated Ringer's, Na bicarbonate 5% soln.

Patients with Zollinger-Ellison syndrome or other hypersecretory conditions: Ranitidine should be diluted to a concentration ≤2.5 mg/mL with dextrose 5% or NaCl 0.9%, lactated Ringer's, Na bicarbonate 5% soln.

Side Effects

Insomnia, mydriasis, cycloplegia, increased ocular tension, urinary hesitancy, palpitations, dyspnea.

In patients taking Mefenamic acid or other NSAIDs, the most frequently reported adverse experiences include : abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers, vomiting, abnormal renal function, anaemia, dizziness, oedema, elevated liver enzymes, headache, increased bleeding time, pruritus, rash and tinnitus.

Ranitidine is well tolerated and side effects are usually uncommon. Altered bowel habit, dizziness, rash, tiredness, reversible confusional states, headache, decreased blood counts, muscle or joint pain have rarely been reported.

Toxicity

Patients experiencing an overdose may present with headache, nausea, vomiting, blurred vision, dilated pupils, dizziness, dry mouth, difficulty swallowing, CNS stimulation, as well as hot, dry skin. Treat patients with gastric lavage, emetics, activated charcoal, sedatives for excitement, and a cholinergic agent if indicated.

The oral LD₅₀ in mice is 625mg/kg.

Oral, rat LD₅₀: 740 mg/kg. Symptoms of overdose may include severe stomach pain, coffee ground-like vomit, dark stool, ringing in the ears, change in amount of urine, unusually fast or slow heartbeat, muscle weakness, slow or shallow breathing, confusion, severe headache or loss of consciousness.

Oral doses of 1,000 mg/kg in mice and rats were not found to be lethal. Intravenous LD50 values in mice and rats were 77 and 83 mg/kg, respectively.

Overdose information

There has been limited experience with ranitidine overdose. Reported acute ingestions of up to 18 grams orally were followed by temporary adverse effects similar to the normal adverse effects of this drug, including tachycardia, bradycardia, dizziness, diarrhea, nausea, and vomiting, among other effects. Gait abnormalities and hypotension have also been observed. When an overdose with ranitidine is suspected, remove unabsorbed ranitidine from the gastrointestinal tract if possible, and monitor the patient and provide supportive therapy as required.

Precaution

Use with caution in patients with autonomic neuropathy, hepatic or renal disease, ulcerative colitis, coronary heart disease, congestive heart failure, cardiac tachyarrhythmia, known or suspected prostatic hypertrophy.

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. To minimise the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. In cases with pre-existing advanced kidney disease, treatment with Mefenamic acid is not recommended.

Ranitidine should be given in reduced dosage to patients with impaired renal and hepatic function.

Interaction

The following agents may increase certain actions or side-effects of Dicycloverine-antiarrhythmic agents, antihistamines, antipsychotic agents, benzodiazepines, MAO inhibitors, narcotic analgesics, nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants and other drugs having anticholinergic activity.

Concomitant use with CYP2C9 isoenzyme inhibitors may alter safety and efficacy of mefenamic acid. May enhance methotrexate toxicity. Reduced BP response to ACE inhibitors or angiotensin II receptor antagonists. Increased risk of serious GI events with aspirin. May reduce the natriuretic effects of furosemide or thiazide diuretics. Reduced renal lithium clearance and elevated plasma lithium levels. May enhance anticoagulant effect of warfarin.

Delayed absorption and increased peak serum concentration with propantheline bromide. Ranitidine minimally inhibits hepatic metabolism of coumarin anticoagulants, theophylline, diazepam and propanolol. May alter absorption of pH-dependent drugs (e.g. ketoconazole, midazolam, glipizide). May reduce bioavailability with antacids.

Volume of Distribution

The volume of distribution for a 20mg oral dose is 3.65L/kg.

• 1.06 L/kg [Normal Healthy Adults (18-45 yr)]

The volume of distribution is higher than body volume, and measures at approximately 1.4 L/kg. It concentrates in breast milk, but does not readily distribute into the cerebrospinal fluid.

Elimination Route

The bioavailability of dicyclomine has not been determined, though it is likely well absorbed as the primary route of elimination is in the urine. Dicyclomine has a T_max of 1-1.5h.

Mefenamic acid is rapidly absorbed after oral administration.

Ranitidine is rapidly absorbed with peak concentrations reached within 1-3 hours after administration, and varying greatly among patients. Bioavailability is about 50%-60% due to hepatic metabolism. In a pharmacokinetic study of healthy males, the AUC 0-infinity was about 2,488.6 ng x h/mL and the median Tmax was 2.83 hours. Food or antacids have limited effects on absorption. One clinical study found that the administration of a potent antacid (150 mmol) in subjects in the fasted state led to decreased absorption of ranitidine.

Half Life

The mean plasma elimination half life is approximately 1.8 hours.

2 hours

The elimination half-life or ranitidine is about 2.5-3 hours. It may be longer after oral administration versus injection. The plasma half-life is longer for elderly patients population due to a decrease in renal function, and is measured at 3-4 hours.

Clearance

Data regarding the clearance of dicyclomine is not readily available.

• Oral cl=21.23 L/hr [Healthy adults (18-45 yrs)]

Renal clearance is about 410 mL/min according to FDA prescribing information. Another resource mentions a plasma clearance of approximately 600 ml/min. Clearance is decreased in the elderly and those with impaired or hepatic renal function. It is recommended to decrease the dose of ranitidine by one-half in patients with renal impairment.

Elimination Route

Dicyclomine is 79.5% eliminated in the urine and 8.4% in the feces.

The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination.

This drug is mainly excreted in the urine but also excreted in the feces. About 30% of a single oral dose has been measured in the urine as unchanged drug within 24 hours of ingestion.

Pregnancy & Breastfeeding use

Pregnancy: Category B. Dicycloverine was neither teratogenic nor embryocidal in animal trial. It, like other drugs should be used during pregnancy only if clearly needed. There are no data on the secretion of this drug into breast milk. Dicycloverine should be used cautiously in case of lactating mother.

Pregnancy: In late pregnancy, as with other NSAIDs, Mefenamic acid should be avoided because it may cause premature closure of the ductus arteriosus. In general there are no adequate and well controlled studies in pregnant women. Mefenamic acid should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Rated as Pregnancy Category C.

Lactation: Trace amounts of Mefenamic acid may be present in breast milk. Taking into account the importance of the drug to the mother , decision should be made whether to discontinue nursing or to discontinue the drug.

Pregnancy: Ranitidine crosses the placenta. But there is no evidence of impaired fertility or harm to the foetus due to Ranitidine. Like other drugs, Ranitidine should only be used during pregnancy if considered essential.

Lactation: Ranitidine is excreted in human breast milk. Caution should be exercised when the drug is administered to a nursing mother.

Contraindication

Dicycloverine is contraindicated in:

• Obstructive uropathy
• Obstructive disease of the gastrointestinal tract
• Severe ulcerative colitis
• Reflux esophagitis
• Unstable cardiovascular status in acute hemorrhage
• Glaucoma
• Myasthenia gravis
• Evidence of prior hypersensitivity to dicycloverine hydrochloride or other ingredients of this formulation
• Infants less than 6 months of age

Mefenamic acid is contraindicated in patients with known hypersensitivity to Me Mefenamic acid acid. Mefenamic acid should not be given to patients who have experienced asthma, urticaria, or allergic type reactions after taking aspirin or other NSAIDs. Rarely fatal, anaphylactic like reactions to NSAIDs have been reported in such patients. Mefenamic acid is contraindicated in patients with active ulceration or chronic inflammation of upper gastrointestinal tract and should not be used in patients with preexisting renal disease.

Patients hypersensitive to Ranitidine

Special Warning

Use in elderly patients: In clinical trial the ulcer healing rates have been found similar in patients age 65 and over with those in younger patients. Additionally, there was no difference in the incidence of adverse effects.

Acute Overdose

Toxic reaction seldom occurs with dicycloverine. The signs and symptoms of overdosage are headache; nausea; vomiting; blurred vision; dilated pupils; hot, dry skin; dizziness; dryness of the mouth; difficulty in swallowing; and CNS stimulation.

Symptoms: Headache, nausea, vomiting, epigastric pain, GI bleeding. Rarely, diarrhoea, disorientation, excitation, coma, drowsiness, tinnitus, fainting, and occasionally convulsions.

Management: Symptomatic and supportive treatment. In acute overdosage, empty the stomach immediately by inducing emesis or by gastric lavage followed by admin of activated charcoal.

Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage with the drug. Symptomatic and supportive therapy should be given as appropriate. If required, the drug may be removed from the plasma by haemodiaiysis.

Storage Condition

Store below 30°C.

Store between 20-25° C.

Store in a cool and dry place. protect from light.

Innovators Monograph

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