Diclotal may be available in the countries listed below.
Diclofenac sodium salt (a derivative of Diclofenac) is reported as an ingredient of Diclotal in the following countries:
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Alertop may be available in the countries listed below.
Cetirizine is reported as an ingredient of Alertop in the following countries:
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Relieving congestion, cough, and throat and airway irritation due to colds, flu, or hay fever. It may also be used for other conditions as determined by your doctor.
Dextromethorphan/Guaifenesin/Phenylephrine Drops are a decongestant, cough suppressant, and expectorant combination. It works by constricting blood vessels and reducing swelling in the nasal passages, loosening mucus and lung secretions in the chest, and making coughs more productive. It also works in the brain to help decrease the cough reflex to reduce a dry cough.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Dextromethorphan/Guaifenesin/Phenylephrine Drops. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Dextromethorphan/Guaifenesin/Phenylephrine Drops. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Dextromethorphan/Guaifenesin/Phenylephrine Drops may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Dextromethorphan/Guaifenesin/Phenylephrine Drops as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Dextromethorphan/Guaifenesin/Phenylephrine Drops.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Dizziness; excitability; headache; nausea; nervousness or anxiety; trouble sleeping; weakness.
Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); difficulty urinating; fast or irregular heartbeat; hallucinations; seizures; severe dizziness, lightheadedness, or headache; tremor.
This is not a complete list of all side effects that may occur. If you have questions or need medical advice about side effects, contact your doctor or health care provider. You may report side effects to the FDA at 1-800-FDA-1088 (1-800-332-1088) or at http://www.fda.gov/medwatch.
See also: Dextromethorphan/Guaifenesin/Phenylephrine side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center (http://www.aapcc.org/DNN/), or emergency room immediately. Symptoms may include blurred vision; confusion; hallucinations; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; unusually fast, slow, or irregular heartbeat; vomiting.
Store Dextromethorphan/Guaifenesin/Phenylephrine Drops at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Dextromethorphan/Guaifenesin/Phenylephrine Drops out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Dextromethorphan/Guaifenesin/Phenylephrine Drops. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Neo-Omnipen may be available in the countries listed below.
Ticlopidine hydrochloride (a derivative of Ticlopidine) is reported as an ingredient of Neo-Omnipen in the following countries:
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In the US, Haemate P is a member of the drug class miscellaneous coagulation modifiers and is used to treat Hemophilia A and von Willebrand's Disease.
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Coagulation Factor VIII , Human (rDNA) Octocog Alfa (a derivative of Coagulation Factor VIII , Human (rDNA)) is reported as an ingredient of Haemate P in the following countries:
Coagulation Factor VIII, Human is reported as an ingredient of Haemate P in the following countries:
Von Willebrand Factor, Human is reported as an ingredient of Haemate P in the following countries:
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Glossary
| SPC | Summary of Product Characteristics (UK) |
Zoolobelin may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Lobeline hydrochloride (a derivative of Lobeline) is reported as an ingredient of Zoolobelin in the following countries:
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FOR DERMATOLOGIC USE ONLY.
NOT FOR USE IN EYES.
DERMATOP® Emollient Cream (prednicarbate emollient cream) 0.1% contains prednicarbate, a synthetic corticosteroid for topical dermatologic use. The chemical name of prednicarbate is 11β, 17, 21-trihydroxypregna-1,4-diene- 3,20-dione 17-(ethyl carbonate) 21-propionate. Prednicarbate has the empirical formula C27H36O8 and a molecular weight of 488.58. Topical corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents.
The CAS Registry Number is 73771-04-7. The chemical structure is:
Prednicarbate is a practically odorless white to yellow-white powder insoluble to practically insoluble in water and freely soluble in ethanol.
Each gram of DERMATOP Emollient Cream 0.1% contains 1.0 mg of prednicarbate in a base consisting of white petrolatum USP, purified water USP, isopropyl myristate NF, lanolin alcohols NF, mineral oil USP, cetostearyl alcohol NF, aluminum stearate, edetate disodium USP, lactic acid USP, and magnesium stearate DAB 9.
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Use of occlusive dressings with hydrocortisone for up to 24 hours have not been shown to increase penetration; however, occlusion of hydrocortisone for 96 hours does markedly enhance penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.
Studies performed with DERMATOP Emollient Cream (prednicarbate emollient cream) 0.1 % indicate that the drug product is in the medium range of potency compared with other topical corticosteroids.
DERMATOP Emollient Cream 0.1% is a medium-potency corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses. DERMATOP Emollient Cream 0.1% may be used with caution in pediatric patients 1 year of age or older. The safety and efficacy of drug use for longer than 3 weeks in this population have not been established. Since safety and efficacy of DERMATOP Emollient Cream 0.1% have not been established in pediatric patients below 1 year of age, its use in this age group is not recommended.
DERMATOP Emollient Cream 0.1% is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparations.
Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.
Patients applying a topical steroid to a large surface area or under occlusion should be evaluated periodically for evidence of HPA-axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. DERMATOP Emollient Cream 0.1% did not produce significant HPA-axis suppression when used at a dose of 30g/day for a week in 10 adult patients with extensive psoriasis or atopic dermatitis. DERMATOP Emollient Cream 0.1% did not produce HPA-axis suppression in any of 59 pediatric patients with extensive atopic dermatitis when applied BID for 3 weeks to > 20% of the body surface (See PRECAUTIONS, Pediatric Use.)
If HPA-axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of the application, or to substitute a less potent corticosteroid. Recovery of HPA-axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. (See PRECAUTIONS, Pediatric Use.)
If irritation develops, DERMATOP Emollient Cream 0.1% should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation, as observed with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.
If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used.
If a favorable response does not occur promptly, use of DERMATOP Emollient Cream 0.1% should be discontinued until the infection has been adequately controlled.
Patients using topical corticosteroids should receive the following information and instructions:
As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within two weeks, contact the physician.
The following tests may be helpful in evaluating patients for HPA-axis suppression:
ACTH stimulation test
A.M. plasma cortisol test
Urinary free cortisol test
In a study of the effect of prednicarbate on fertility, pregnancy, and postnatal development in rats, no effect was noted on the fertility or pregnancy of the parent animals or postnatal development of the offspring after administration of up to 0.80 mg/kg of prednicarbate subcutaneously.
Prednicarbate has been evaluated in the Salmonella reversion test (Ames test) over a wide range of concentrations in the presence and absence of an S-9 liver microsomal fraction, and did not demonstrate mutagenic activity. Similarly, prednicarbate did not produce any significant changes in the numbers of micronuclei seen in erythrocytes when mice were given doses ranging from 1 to 160 mg/kg of the drug.
Pregnancy Category C
Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.
Prednicarbate has been shown to be teratogenic and embryotoxic in Wistar rats and Himalayan rabbits when given subcutaneously during gestation at doses 1900 times and 45 times the recommended topical human dose, assuming a percutaneous absorption of approximately 3%. In the rats, slightly retarded fetal development and an incidence of thickened and wavy ribs higher than the spontaneous rate were noted.
In rabbits, increased liver weights and slight increase in the fetal intrauterine death rate were observed. The fetuses that were delivered exhibited reduced placental weight, increased frequency of cleft palate, ossification disorders in the sternum, omphalocele, and anomalous posture of the forelimbs.
There are no adequate and well-controlled studies in pregnant women on teratogenic effects of prednicarbate. DERMATOP Emollient Cream (prednicarbate emollient cream) 0.1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when DERMATOP Emollient Cream 0.1% is administered to a nursing woman.
DERMATOP Emollient Cream 0.1% may be used with caution in pediatric patients 1 year of age or older, although the safety and efficacy of drug use longer than 3 weeks have not been established. The use of DERMATOP Emollient Cream (prednicarbate emollient cream) 0.1% is supported by results of a three-week, uncontrolled study in 59 pediatric patients between the ages of 4 months and 12 years of age with atopic dermatitis. None of the 59 pediatric patients showed evidence of HPA-axis suppression. Safety and efficacy of DERMATOP Emollient Cream 0.1% in pediatric patients below 1 year of age have not been established, therefore use in this age group is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA-axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. In an uncontrolled study in pediatric patients with atopic dermatitis, the incidence of adverse reactions possibly or probably associated with the use of DERMATOP Emollient Cream 0.1% was limited.
Mild signs of atrophy developed in 5 patients (5/59, 8%) during the clinical trial, with 2 patients exhibiting more than one sign. Two patients (2/59, 3%) developed shininess, and two patients (2/59, 3%) developed thinness. Three patients (3/59, 5%) were observed with mild telangiectasia. It is unknown whether prior use of topical corticosterioids was a contributing factor in the development of telangiectasia in 2 of the patients. Adverse effects including striae have also been reported with inappropriate use of topical corticosteroids in infants and children. Pediatric patients applying topical corticosteroids to greater than 20% of body surface are at higher risk for HPA-axis suppression.
HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
DERMATOP Emollient Cream 0.1% should not be used in the treatment of diaper dermatitis.
In controlled adult clinical studies, the incidence of adverse reactions probably or possibly associated with the use of DERMATOP Emollient Cream 0.1% was approximately 4%. Reported reactions included mild signs of skin atrophy in 1% of treated patients, as well as the following reactions which were reported in less than 1% of patients: pruritis, edema, paresthesia, urticaria, burning, allergic contact dermatitis and rash.
In an uncontrolled study in pediatric patients with atopic dermatitis, the incidence of adverse reactions possibly or probably associated with the use of DERMATOP Emollient Cream 0.1 % was limited. Mild signs of atrophy developed in 5 patients (5/59, 8%) during the clinical trial, with 2 patients exhibiting more than one sign. Two patients (2/59, 3%) developed shininess, and 2 patients (2/59, 3%) developed thinness. Three patients (3/59, 5 %) were observed with mild telangiectasia. It is unknown whether prior use of topical corticosteroids was a contributing factor in the development of telangiectasia in 2 of the patients (See PRECAUTIONS, Pediatric Use.)
The following additional local adverse reactions have been reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, secondary infection, striae and miliaria.
Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)
Apply a thin film of DERMATOP Emollient Cream (prednicarbate emollient cream) 0.1% to the affected skin areas twice daily. Rub in gently.
DERMATOP Emollient Cream (prednicarbate emollient cream) 0.1 % may be used in pediatric patients 1 year of age or older. Safety and efficacy of DERMATOP Emollient Cream 0.1% in pediatric patients for more than 3 weeks of use have not been established. Use in pediatric patients under 1 year of age is not recommended.
As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary.
DERMATOP Emollient Cream 0.1% should not be used with occlusive dressings unless directed by the physician. DERMATOP Emollient Cream 0.1% should not be applied in the diaper area if the child still requires diapers or plastic pants as these garments may constitute occlusive dressing.
DERMATOP Emollient Cream (prednicarbate emollient cream) 0.1% is supplied in 60 g (NDC 0066-0507-60) tubes.
Store between 41 and 77°F (5 and 25°C).
Dermik Laboratories
a business of sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
Revised January 2011
© 2011 sanofi-aventis U.S. LLC
NDC 0066-0507-60
DERMATOP® Emollient Cream
prednicarbate emollient cream 0.1%
FOR DERMATOLOGIC USE ONLY — NOT FOR USE IN EYES
One 60g Tube
DERMIK®
sanofi aventis
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NDA | NDA020279 | 10/29/1993 | |
| Labeler - Dermik Laboratories (824676584) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| sanofi-aventis Deutschland GmbH | 313218430 | MANUFACTURE, ANALYSIS, API MANUFACTURE, LABEL, PACK | |
Brivumen may be available in the countries listed below.
Brivudine is reported as an ingredient of Brivumen in the following countries:
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Ultralan Crinale Solüsyon may be available in the countries listed below.
Fluocortolone 21-pivalate (a derivative of Fluocortolone) is reported as an ingredient of Ultralan Crinale Solüsyon in the following countries:
Salicylic Acid is reported as an ingredient of Ultralan Crinale Solüsyon in the following countries:
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Oxofenil may be available in the countries listed below.
Minoxidil is reported as an ingredient of Oxofenil in the following countries:
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Nelfinavir Mesylate may be available in the countries listed below.
Nelfinavir Mesylate (USAN) is known as Nelfinavir in the US.
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| USAN | United States Adopted Name |
Flogosine may be available in the countries listed below.
Piroxicam is reported as an ingredient of Flogosine in the following countries:
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Calcium beta may be available in the countries listed below.
Calcium Carbonate is reported as an ingredient of Calcium beta in the following countries:
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Dolosal may be available in the countries listed below.
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Acidosan may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Sodium Bicarbonate is reported as an ingredient of Acidosan in the following countries:
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Niazol may be available in the countries listed below.
Naphazoline nitrate (a derivative of Naphazoline) is reported as an ingredient of Niazol in the following countries:
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Ansietyl may be available in the countries listed below.
Alprazolam is reported as an ingredient of Ansietyl in the following countries:
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Tolfédine may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Tolfenamic Acid is reported as an ingredient of Tolfédine in the following countries:
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Meglumine Iotalamate may be available in the countries listed below.
Meglumine Iotalamate (BANM) is also known as Iotalamic Acid (Rec.INN)
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| BANM | British Approved Name (Modified) |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Arodate may be available in the countries listed below.
Gabexate mesilate (a derivative of Gabexate) is reported as an ingredient of Arodate in the following countries:
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Salsoroitin S may be available in the countries listed below.
Chondroitin Polysulfate sodium salt (a derivative of Chondroitin Polysulfate) is reported as an ingredient of Salsoroitin S in the following countries:
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Bromélaïnes may be available in the countries listed below.
Bromélaïnes (DCF) is also known as Bromelains (Rec.INN)
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Glossary
| DCF | Dénomination Commune Française |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Ampiplus may be available in the countries listed below.
Ampicillin sodium salt (a derivative of Ampicillin) is reported as an ingredient of Ampiplus in the following countries:
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Mainnox may be available in the countries listed below.
Dicycloverine hydrochloride (a derivative of Dicycloverine) is reported as an ingredient of Mainnox in the following countries:
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Maliasin may be available in the countries listed below.
Barbexaclone is reported as an ingredient of Maliasin in the following countries:
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Kanakion may be available in the countries listed below.
Phytomenadione is reported as an ingredient of Kanakion in the following countries:
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Tenopt may be available in the countries listed below.
Timolol maleate (a derivative of Timolol) is reported as an ingredient of Tenopt in the following countries:
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Timolol-1A Pharma may be available in the countries listed below.
Timolol maleate (a derivative of Timolol) is reported as an ingredient of Timolol-1A Pharma in the following countries:
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Almag may be available in the countries listed below.
Aluminium Hydroxide is reported as an ingredient of Almag in the following countries:
Magnesium Trisilicate is reported as an ingredient of Almag in the following countries:
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Pyme Cinazin may be available in the countries listed below.
Cinnarizine is reported as an ingredient of Pyme Cinazin in the following countries:
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Urisec may be available in the countries listed below.
Urea is reported as an ingredient of Urisec in the following countries:
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Atropin-POS may be available in the countries listed below.
Atropine sulfate (a derivative of Atropine) is reported as an ingredient of Atropin-POS in the following countries:
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Topigen may be available in the countries listed below.
Topiramate is reported as an ingredient of Topigen in the following countries:
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In the US, Xopenex (levalbuterol systemic) is a member of the drug class adrenergic bronchodilators and is used to treat Asthma - acute, Asthma - Maintenance, COPD - Acute and COPD - Maintenance.
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Levosalbutamol hydrochloride (a derivative of Levosalbutamol) is reported as an ingredient of Xopenex in the following countries:
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Sedarest may be available in the countries listed below.
Estazolam is reported as an ingredient of Sedarest in the following countries:
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Ranitidine hydrochloride (HCl), is a histamine H2-receptor antagonist. Chemically it is N - [2 - [[[5 - [(dimethylamino)methyl] - 2 - furanyl]methyl]thio]ethyl] - N’ - methyl - 2 - nitro - 1,1 - ethenediamine, HCl.
It has the following structure:
The empirical formula is C13H22N4O3S • HCl, representing a molecular weight of 350.87.
Ranitidine HCl is a white to pale yellow, granular substance that is soluble in water. It has a slightly bitter taste and sulfur like odor.
Each tablet, for oral administration contains 168 mg or 336 mg of Ranitidine hydrochloride equivalent to 150 mg and 300 mg of Ranitidine, respectively. Inactive ingredients: D & C Red #30 Aluminum Lake, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, triethyl citrate, sodium starch glycolate, titanium dioxide and flavoring. The 300 mg also contains: D & C Yellow #10 Aluminum Lake.
Each capsule, for oral administration contains 168 mg or 336 mg of Ranitidine hydrochloride equivalent to 150 mg and 300 mg of Ranitidine, respectively. Inactive ingredients: Ammonium hydroxide, colloidal silicon dioxide, corn starch, FD & C Blue #1, FD & C Red #40, FD & C Yellow #6, gelatin, magnesium stearate, pharmaceutical glaze, propylene glycol, silicon dioxide, simethicone, sodium lauryl sulfate, sodium starch glycolate, and titanium dioxide.
Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells. Ranitidine does not lower serum Ca++ in hypercalcemic states. Ranitidine is not a anticholinergic agent.
Ranitidine tablets and Ranitidine capsules are 50% absorbed after oral administration, compared to an intravenous (IV) injection with mean peak levels of 440 to 545 ng/mL occurring 2 to 3 hours after a 150 mg dose. Absorption is not significantly impaired by the administration of food or antacids. Propantheline slightly delays and increases peak blood levels of Ranitidine, probably by delaying gastric emptying and transit time. In one study, simultaneous administration of high-potency antacid (150 mmol) in fasting subjects has been reported to decrease the absorption of Ranitidine.
The volume of distribution is about 1.4 L/kg. Serum protein binding averages 15%.
In humans, the N-oxide is the principal metabolite in the urine; however, this amounts to <4% of the dose. Other metabolites are the S-oxide (1%) and the desmethyl Ranitidine (1%). The remainder of the administered dose is found in the stool. Studies in patients with hepatic dysfunction (compensated cirrhosis) indicate that there are minor, but clinically insignificant, alterations in Ranitidine half-life, distribution, clearance, and bioavailability.
The principal route of excretion is the urine, with approximately 30% of the orally administered dose collected in the urine as unchanged drug in 24 hours. Renal clearance is about 410 mL/min, indicating active tubular excretion. The elimination half-life is 2.5 to 3 hours. Four patients with clinically significant renal function impairment (creatinine clearance 25 to 35 mL/min) administered 50 mg of Ranitidine intravenously had an average plasma half-life of 4.8 hours, a Ranitidine clearance of 29 mL/min, and a volume of distribution of 1.76 L/kg. In general, these parameters appear to be altered in proportion to creatinine clearance (see DOSAGE AND ADMINISTRATION).
The plasma half-life is prolonged and total clearance is reduced in the elderly population due to a decrease in renal function. The elimination half-life is 3 to 4 hours. Peak levels average 526 ng/mL following a 150 mg twice daily dose and occur in about 3 hours (see PRECAUTIONS: Geriatric Use and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients with Impaired Renal Function).
There are no significant differences in the pharmacokinetic parameter values for Ranitidine in pediatric patients (from 1 month up to 16 years of age) and healthy adults when correction is made for body weight. The average bioavailability of Ranitidine given orally to pediatric patients is 48% which is comparable to the bioavailability of Ranitidine in the adult population. All other pharmacokinetic parameter values (t1/2, Vd, and CL) are similar to those observed with intravenous Ranitidine use in pediatric patients. Estimates of Cmax and Tmax are displayed in Table 1.
| Population(age) | n | Dosage Form (dose) | Cmax (ng/mL) | Tmax (hours) |
Gastric or duodenal ulcer (3.5 to 16 years) | 12 | Tablets (1 to 2 mg/kg) | 54 to 492 | 2.0 |
Otherwise healthy requiring Ranitidine (0.7 to 14 years, Single dose) | 10 | Syrup (2 mg/kg) | 244 | 1.61 |
Otherwise healthy requiring Ranitidine (0.7 to 14 years, Multiple dose) | 10 | Syrup (2 mg/kg) | 320 | 1.66 |
Plasma clearance measured in two neonatal patients (less than 1 month of age) was considerably lower (3 mL/min/kg) than children or adults and is likely due to reduced renal function observed in this population (see PRECAUTIONS: Pediatric Useand DOSAGE AND ADMINISTRATION: Pediatric Use).
Serum concentrations necessary to inhibit 50% of stimulated gastric acid secretion are estimated to be 36 to 94 ng/mL. Following a single oral dose of 150 mg, serum concentrations of Ranitidine are in this range up to 12 hours. However, blood levels bear no consistent relationship to dose or degree of acid inhibition.
Ranitidine inhibits both daytime and nocturnal basal gastric acid secretions as well as gastric acid secretion stimulated by food, betazole, and pentagastrin, as shown in Table 2.
Time after Dose, h | % Inhibition of Gastric Acid Output by Dose, mg | ||||
| 75-80 | 100 | 150 | 200 | ||
| Basal | Up to 4 | 99 | 95 | ||
| Nocturnal | Up to 13 | 95 | 96 | 92 | |
| Betazole | Up to 3 | 97 | 99 | ||
| Pentagastrin | Up to 5 | 58 | 72 | 72 | 80 |
| Meal | Up to 3 | 73 | 79 | 95 | |
It appears that basal-, nocturnal-, and betazole-stimulated secretions are most sensitive to inhibition by Ranitidine, responding almost completely to doses of 100 mg or less, while pentagastrin- and food-stimulated secretions are more difficult to suppress.
Ranitidine does not affect pepsin secretion. Total pepsin output is reduced in proportion to the decrease in volume of gastric juice.
Ranitidine has no significant effect on pentagastrin-stimulated intrinsic factor secretion.
Ranitidine has little or no effect on fasting or postprandial serum gastrin.
a. Gastric bacterial flora – increase in nitrate-reducing organisms, significance not known.
b. Prolactin levels – no effect in recommended dosage.
c. Other pituitary hormones – no effect on serum gonadotropins, TSH, or GH. Possible impairment of vasopressin release.
d. No change in cortisol, aldosterone, androgen, or estrogen levels.
e. No antiandrogenic action.
f. No effect on count, motility, or morphology of sperm.
Oral doses of 6 to 10 mg/kg per day in two or three divided doses maintain gastric pH>4 throughout most of the dosing interval.
In a multicenter, double-blind, controlled, US study of endoscopically diagnosed duodenal ulcers, earlier healing was seen in the patients treated with Ranitidine as shown in Table 3.
| ||||
| Ranitidine* | Placebo* | |||
Number Entered | Healed/ Evaluable | Number Entered | Healed/ Evaluable | |
Outpatients Week 2 | 69/182 | 31/164 | ||
| (38%)† | (19%) | |||
| 195 | 188 | |||
| Week 4 | 137/187 | 76/168 | ||
| (73%)† | (45%) | |||
In these studies, patients treated with Ranitidine reported a reduction in both daytime and nocturnal pain, and they also consumed less antacid than the placebo-treated patients.
| Ulcer Healed | Ulcer Not Healed | |
| Ranitidine | 0.06 | 0.71 |
| Placebo | 0.71 | 1.43 |
Foreign studies have shown that patients heal equally well with 150 mg two times a day and 300 mg at bedtime (85% versus 84%, respectively) during a usual 4-week course of therapy. If patients require extended therapy of 8 weeks, the healing rate may be higher for 150 mg two times a day as compared to 300 mg at bedtime (92% versus 87%, respectively).
Studies have been limited to short-term treatment of acute duodenal ulcer. Patients whose ulcers healed during therapy had recurrences of ulcers at the usual rates.
Ranitidine has been found to be effective as maintenance therapy for patients following healing of acute duodenal ulcers. In two independent, double-blind, multicenter, controlled trials, the number of duodenal ulcers observed was significantly less in patients treated with Ranitidine (150 mg at bedtime) than in patients treated with placebo over a 12-month period.
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| Double-blind, Multicenter, Placebo-Controlled Trials | |||||
Multicenter Trial | Drug | Duodenal Ulcer Prevalence | No. of Patients | ||
0-4 Months | 0-8 Months | 0-12 Months | |||
| RAN* | 20%†‡ | 24%†‡ | 35%†‡ | 138 | |
| USA | PLC§ | 44%† | 54%† | 59%† | 139 |
| RAN* | 12%†‡ | 21%†‡ | 28%†‡ | 174 | |
| Foreign | PLC§ | 56%† | 64%† | 68%† | 165 |
As with other H2-antagonists, the factors responsible for the significant reduction in the prevalence of duodenal ulcers include prevention of recurrence of ulcers, more rapid healing of ulcers that may occur during maintenance therapy, or both.
In a multicenter, double-blind, controlled, US study of endoscopically diagnosed gastric ulcers, earlier healing was seen in the patients treated with Ranitidine as shown in Table 6.
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| Ranitidine* | Placebo* | |||
Number Entered | Healed/ Evaluable | Number Entered | Healed/ Evaluable | |
Outpatients Week 2 | 92 | 16/83 (19%) | 94 | 10/83 (12%) |
| Week 6 | 50/73 (68%)† | 35/69 (51%) | ||
In this multicenter trial, significantly more patients treated with Ranitidine became pain free during therapy.
In two multicenter, double-blind, randomized, placebo-controlled, 12-month trials conducted in patients whose gastric ulcers had been previously healed, Ranitidine tablets or Ranitidine capsules 150 mg at bedtime were significantly more effective than placebo in maintaining healing of gastric ulcers.
Ranitidine inhibits gastric acid secretion and reduces occurrence of diarrhea, anorexia, and pain in patients with pathological hypersecretion associated with Zollinger-Ellison syndrome, systemic mastocytosis, and other pathological hypersecretory conditions (e.g., postoperative, “short-gut” syndrome, idiopathic). Use of Ranitidine was followed by healing of ulcers in 8 of 19 (42%) patients who were intractable to previous therapy.
In two multicenter, double-blind, placebo-controlled, 6-week trials performed in the United States and Europe, Ranitidine 150 mg two times a day was more effective than placebo for the relief of heartburn and other symptoms associated with GERD. Ranitidine-treated patients consumed significantly less antacid than did placebo-treated patients.
The US trial indicated that Ranitidine 150 mg two times a day significantly reduced the frequency of heartburn attacks and severity of heartburn pain within 1 to 2 weeks after starting therapy. The improvement was maintained throughout the 6-week trial period. Moreover, patient response rates demonstrated that the effect on heartburn extends through both the day and night time periods.
In two additional US multicenter, double-blind, placebo-controlled, 2-week trials, Ranitidine 150 mg two times a day was shown to provide relief of heartburn pain within 24 hours of initiating therapy and a reduction in the frequency and severity of heartburn.
In two multicenter, double-blind, randomized, placebo-controlled, 12-week trials performed in the United States, Ranitidine 150 mg 4 times daily was significantly more effective than placebo in healing endoscopically diagnosed erosive esophagitis and in relieving associated heartburn. The erosive esophagitis healing rates were as follows:
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| Healed/Evaluable | ||||
Placebo* (n = 229) | Ranitidine 150 mg 4 times daily* (n = 215) | |||
| Week 4 | 43/198 | (22%) | 96/206 | (47%)† |
| Week 8 | 63/176 | (36%) | 142/200 | (71%)† |
| Week 12 | 92/159 | (58%) | 162/192 | (84%)† |
No additional benefit in healing of esophagitis or in relief of heartburn was seen with a Ranitidine dose of 300 mg 4 times daily.
In two multicenter, double-blind, randomized, placebo-controlled, 48-week trials conducted in patients whose erosive esophagitis had been previously healed, Ranitidine 150 mg two times a day was significantly more effective than placebo in maintaining healing of erosive esophagitis.
Ranitidine is indicated in:
Concomitant antacids should be given as needed for pain relief to patients with active duodenal ulcer; active, benign gastric ulcer; hypersecretory states; GERD; and erosive esophagitis.
Ranitidine is contraindicated in patients known to have hypersensitivity to the drug or any of the ingredients (see PRECAUTIONS).
False-positive tests for urine protein with Multistix® may occur during Ranitidine therapy, and therefore testing with sulfosalicylic acid is recommended.
Ranitidine has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.
Procainamide: Ranitidine, a substrate of the renal organic cation transport system, may affect the clearance of other drugs eliminated by this route. High doses of Ranitidine (e.g., such as those used in the treatment of Zollinger-Ellison syndrome) have been shown to reduce the renal excretion of procainamide and N-acetylprocainamide resulting in increased plasma levels of these drugs. Although this interaction is unlikely to be clinically relevant at usual Ranitidine doses, it may be prudent to monitor for procainamide toxicity when administered with oral Ranitidine at a dose exceeding 300 mg per day.
Warfarin: There have been reports of altered prothrombin time among patients on concomitant warfarin and Ranitidine therapy. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with Ranitidine.
Ranitidine may alter the absorption of drugs in which gastric pH is an important determinant of bioavailability. This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib). Appropriate clinical monitoring is recommended.
Atazanavir: Atazanavir absorption may be impaired based on known interactions with other agents that increase gastric pH. Use with caution. See atazanavir label for specific recommendations.
Delavirdine: Delavirdine absorption may be impaired based on known interactions with other agents that increase gastric pH. Chronic use of H2-receptor antagonists with delavirdine is not recommended.
Gefitinib: Gefitinib exposure was reduced by 44% with the coadministration of Ranitidine and sodium bicarbonate (dosed to maintain gastric pH above 5.0). Use with caution.
Glipizide: In diabetic patients, glipizide exposure was increased by 34% following a single 150-mg dose of oral Ranitidine. Use appropriate clinical monitoring when initiating or discontinuing Ranitidine.
Ketoconazole: Oral ketoconazole exposure was reduced by up to 95% when oral Ranitidine was coadministered in a regimen to maintain a gastric pH of 6 or above. The degree of interaction with usual dose of Ranitidine (150 mg twice daily) is unknown.
Midazolam: Oral midazolam exposure in 5 healthy volunteers was increased by up to 65% when administered with oral Ranitidine at a dose of 150 mg twice daily. However, in another interaction study in 8 volunteers receiving IV midazolam, a 300 mg oral dose of Ranitidine increased midazolam exposure by about 9%. Monitor patients for excessive or prolonged sedation when Ranitidine is coadministered with oral midazolam.
Triazolam: Triazolam exposure in healthy volunteers was increased by approximately 30% when administered with oral Ranitidine at a dose of 150 mg twice daily. Monitor patients for excessive or prolonged sedation.
There was no indication of tumorigenic or carcinogenic effects in life-span studies in mice and rats at dosages up to 2,000 mg/kg per day.
Ranitidine was not mutagenic in standard bacterial tests (Salmonella, Escherichia coli) for mutagenicity at concentrations up to the maximum recommended for these assays.
In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of two matings per week for the next 9 weeks.
Reproduction studies have been performed in rats and rabbits at doses up to 160 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Ranitidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Ranitidine is secreted in human milk. Caution should be exercised when Ranitidine is administered to a nursing mother.
The safety and effectiveness of Ranitidine has been established in the age-group of 1 month to 16 years for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease and erosive esophagitis, and the maintenance of healed duodenal and gastric ulcer. Use of Ranitidine in this age-group is supported by adequate and well-controlled studies in adults, as well as additional pharmacokinetic data in pediatric patients and an analysis of the published literature (see CLINICAL PHARMACOLOGY: Pediatrics and DOSAGE AND ADMINISTRATION: Pediatric Use).
Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions or the maintenance of healing of erosive esophagitis have not been established.
Safety and effectiveness in neonates (less than one month of age) have not been established (see CLINICAL PHARMACOLOGY: Pediatrics).
Of the total number of subjects enrolled in US and foreign controlled clinical trials of oral formulations of Ranitidine, for which there were subgroup analyses, 4,197 were 65 and over, while 899 were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients with Impaired Renal Function).
The following have been reported as events in clinical trials or in the routine management of patients treated with Ranitidine. The relationship to therapy with Ranitidine has been unclear in many cases. Headache, sometimes severe, seems to be related to administration of Ranitidine.
Rarely, malaise, dizziness, somnolence, insomnia, and vertigo. Rare cases of reversible mental confusion, agitation, depression, and hallucinations have been reported, predominantly in severely ill elderly patients. Rare cases of reversible blurred vision suggestive of a change in accommodation have been reported. Rare reports of reversible involuntary motor disturbances have been received.
As with other H2-blockers, rare reports of arrhythmias such as tachycardia, bradycardia, atrioventricular block, and premature ventricular beats.
Constipation, diarrhea, nausea/vomiting, abdominal discomfort/pain, and rare reports of pancreatitis.
There have been occasional reports of hepatocellular, cholestatic, or mixed hepatitis, with or without jaundice. In such circumstances, Ranitidine should be immediately discontinued. These events are usually reversible, but in rare circumstances death has occurred. Rare cases of hepatic failure have also been reported. In normal volunteers, SGPT values were increased to at least twice the pretreatment levels in 6 of 12 subjects receiving 100 mg 4 times daily intravenously for 7 days, and in 4 of 24 subjects receiving 50 mg 4 times daily intravenously for 5 days.
Rare reports of arthralgias and myalgias.
Blood count changes (leukopenia, granulocytopenia, and thrombocytopenia) have occurred in a few patients. These were usually reversible. Rare cases of agranulocytosis, pancytopenia, sometimes with marrow hypoplasia, and aplastic anemia and exceedingly rare cases of acquired immune hemolytic anemia have been reported.
Controlled studies in animals and man have shown no stimulation of any pituitary hormone by Ranitidine and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when Ranitidine has been substituted. However, occasional cases of impotence and loss of libido have been reported in male patients receiving Ranitidine, but the incidence did not differ from that in the general population. Rare cases of breast symptoms and conditions, including galactorrhea and gynecomastia, have been reported in both males and females.
Rash, including rare cases of erythema multiforme. Rare cases of alopecia and vasculitis.
A large epidemiological study suggested an increased risk of developing pneumonia in current users of histamine-2-receptor antagonists (H2RAs) compared to patients who had stopped H2RA treatment, with an observed adjusted relative risk of 1.63 (95% CI, 1.07-2.48). However, a causal relationship between use of H2RAs and pneumonia has not been established.
Rare cases of hypersensitivity reactions (e.g., bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic edema, acute interstitial nephritis, and small increases in serum creatinine.
There has been limited experience with overdosage. Reported acute ingestions of up to 18 g orally have been associated with transient adverse effects similar to those encountered in normal clinical experience (see ADVERSE REACTIONS). In addition, abnormalities of gait and hypotension have been reported.
When overdosage occurs, the usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.
Studies in dogs receiving dosages of Ranitidine in excess of 225 mg/kg per day have shown muscular tremors, vomiting, and rapid respiration. Single oral doses of 1,000 mg/kg in mice and rats were not lethal. Intravenous LD50 values in mice and rats were 77 and 83 mg/kg, respectively.
The current recommended adult oral dosage of Ranitidine for duodenal ulcer is 150 mg twice daily. An alternative dosage of 300 mg once daily after the evening meal or at bedtime can be used for patients in whom dosing convenience is important. The advantages of one treatment regimen compared to the other in a particular patient population have yet to be demonstrated (see CLINICAL PHARMACOLOGY: Clinical Trials: Active Duodenal Ulcer). Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in US studies, and several foreign trials have shown that 100 mg twice daily is as effective as the 150 mg dose.
Antacid should be given as needed for relief of pain (see CLINICAL PHARMACOLOGY: Pharmacokinetics).
The current recommended adult oral dosage is 150 mg at bedtime.
The current recommended adult oral dosage is 150 mg twice a day. In some patients it may be necessary to administer Ranitidine 150 mg doses more frequently. Dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. Dosages up to 6 g/day have been employed in patients with severe disease.
The current recommended adult oral dosage is 150 mg twice a day.
The current recommended adult oral dosage is 150 mg at bedtime.
The current recommended adult oral dosage is 150 mg twice a day.
The current recommended adult oral dosage is 150 mg four times a day.
