Ranispas Dv

Uses

Spastic conditions of the gastrointestinal tract, irritable bowel syndrome-

• Biliary colics and spastic conditions of the biliary tract: Cholecystolithiasis, cholecystitis, cholangitis.
• Renal colics and spastic conditions of the urogenital tract: Nephrolithiasis, ureterolithiasis, pyelitis, cystitis.
• Spastic conditions of the uterus: Dysmenorrhea, imminent abortion, uterine tetanus.

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.

Ranispas Dv is also used to associated treatment for these conditions: Abdominal Pain caused by Gall Stones, Abdominal Pain caused by Kidney Stones, Muscle Spasms, Spastic Pain, Spastic Pain caused by Cystitis, Spastic Pain caused by Funicular Nephritis, Spastic Pain caused by Gallbladder disorders, Spastic Pain caused by Physical Examination, Spastic Pain caused by cholecysitis, Spastic Pain of the Gastrointestinal TractAcid 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 Ranispas Dv works

Drotaverine is a selective inhibitor of phosphodiesterase 4 (PDE4), which is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP). Inhibition of PDE4 leads to elevated levels of cAMP, leading to smooth muscle relaxation. Recent research showed that low levels of cAMP have been associated with brain tumorigenesis, leading to the investigation of PDE4 inhibitors as potential anticancer agents.

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

Ranispas Dv dosage

Oral-

• Adults: 1 to 2 tablets, 3 times daily
• Children (over 6 years): 1/2 to 1 tablet, 1-2 times daily.
• Children (1-6 years): 1/4 to 1/2 tablet, 1-2 times daily.

Injection-

• Adults: 1 to 2 ampoules, intramuscularly or subcutaneously, 1-3 times daily.
• For the management of acute stone colics: 1 or 2 ampoules by slow intravenous injection.

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

The common side effects are headache, dizziness, rhinitis, sinusitis, gastrointestinal upset, nausea, pharyngitis, edema and fatigue.

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

Oral LD₅₀ is 540 mg/kg in rats and 350 mg/kg in mice. There is limited information on drotaverine overdose and toxicity.

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

Caution should be taken for patients suffering from liver and kidney disease.

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

Interaction

May attenuate the action of levodopa. Concurrent use of analgesics, antimuscarinics or benzodiazepines. Additive beneficial effect with concurrent use of analgesics, antimuscarinics or benzodiazepines.

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

Following oral administration of a single 80 mg dose, the mean volume of distribution was 193 ± 48 L. Following an intravenous dose of 80 mg, the mean volume of distribution was 195 ± 48 L.

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

Drotaverine is not completely absorbed following oral administration and its bioavailability is highly variable. Following oral administration of a single 80 mg dose, the absolute bioavailability ranged between 24.5 and 91 % with a mean of 58.2 ± 18.2%. Mean C_max was 292 ± 88 ng/mL. Mean AUC was 3251 ± 950 ng*h/mL. Mean T_max was 1.9 ± 0.54 hours.

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

Following oral administration of a single 80 mg dose, the mean half-life was 9.11 ± 1.29 hours. Following an intravenous dose of 80 mg, the mean half-life 9.33 ± 1.02 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

Following oral administration of a single 80 mg dose, the mean renal clearance was 0.59 ± 0.18 mL/min. Following an intravenous dose of 80 mg, the mean renal clearance was 0.73 ± 0.29 mL/min.

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

Drotaverine is mainly eliminated via hepatic metabolism. About 67% of the drug is found in feces and 20% of the drug was eliminated with urine.

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

As with most drugs, the use of Drotaverine Hydrochloride should be avoided during pregnancy and lactation unless essential.

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

Drotaverine is contraindicated in patients with known hypersensitivity to the products and its constituents.

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

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 in a cool and dry place. protect from light.

Innovators Monograph

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