Azithromycin dura may be available in the countries listed below.
Azithromycin dihydrate (a derivative of Azithromycin) is reported as an ingredient of Azithromycin dura in the following countries:
International Drug Name Search
Generic Name: benzocaine (Oral route, Oromucosal route)
BEN-zoe-kane
In the U.S.
In Canada
Available Dosage Forms:
Therapeutic Class: Anesthetic, Local
Chemical Class: Amino Ester
Benzocaine lozenges are used to relieve pain and irritation caused by sore throat, sore mouth, or canker sores.
This medicine is available without a prescription; however, your doctor may have special instructions on the proper use and dose for your medical problem.
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
No information is available on the relationship of age to the effects of benzocaine lozenges in the pediatric population. Safety and efficacy have not been established in children below 5 years of age.
No information is available on the relationship of age to the effects of benzocaine in geriatric patients.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain benzocaine. It may not be specific to Detane. Please read with care.
Use this medicine exactly as directed by your doctor. Do not use more of this medicine, do not use it more often, and do not use it for a longer time than directed. To do so may increase the chance of absorption into the body and the risk of side effects.
This medicine should be used only for problems being treated by your doctor or conditions listed in the package directions. Check with your doctor before using it for other problems, especially if you think that an infection may be present.
Do not use this medicine for more than 2 days without checking first with your doctor.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
If your condition does not improve within 7 days, or if it becomes worse, check with your doctor.
Call your doctor right away if you start to have a severe sore throat or sore throat that occurs with a high fever, headache, nausea, or vomiting. These maybe signs of an infection.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
See also: Detane side effects (in more detail)
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L-Tryptophan-ratiopharm may be available in the countries listed below.
Tryptophan is reported as an ingredient of L-Tryptophan-ratiopharm in the following countries:
International Drug Name Search
Oxalatin may be available in the countries listed below.
Oxaliplatin is reported as an ingredient of Oxalatin in the following countries:
International Drug Name Search
Smokeless may be available in the countries listed below.
Lobeline sulfate (a derivative of Lobeline) is reported as an ingredient of Smokeless in the following countries:
International Drug Name Search
Pymehyospan may be available in the countries listed below.
Scopolamine butylbromide (a derivative of Scopolamine) is reported as an ingredient of Pymehyospan in the following countries:
International Drug Name Search
Normens may be available in the countries listed below.
Norethisterone is reported as an ingredient of Normens in the following countries:
International Drug Name Search
Peptomet may be available in the countries listed below.
Domperidone is reported as an ingredient of Peptomet in the following countries:
Domperidone maleate (a derivative of Domperidone) is reported as an ingredient of Peptomet in the following countries:
International Drug Name Search
In some countries, this medicine may only be approved for veterinary use.
In the US, Danazol (danazol systemic) is a member of the drug class antigonadotropic agents and is used to treat Angioedema, Endometriosis, Evan's Syndrome and Fibrocystic Breast Disease.
US matches:
Prop.INN
G03XA01
0017230-88-5
C22-H27-N-O2
337
Gonadotropin inhibitor
Pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol, (17α)-
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| DCIT | Denominazione Comune Italiana |
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Prop.INN | Proposed International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Rubriment may be available in the countries listed below.
Nicotinic Acid benzyl ester (a derivative of Nicotinic Acid) is reported as an ingredient of Rubriment in the following countries:
International Drug Name Search
Flamistav may be available in the countries listed below.
Stavudine is reported as an ingredient of Flamistav in the following countries:
International Drug Name Search
Sucralfate Teva may be available in the countries listed below.
Sucralfate is reported as an ingredient of Sucralfate Teva in the following countries:
International Drug Name Search
Nimesulide Dorom may be available in the countries listed below.
Nimesulide is reported as an ingredient of Nimesulide Dorom in the following countries:
International Drug Name Search
Cardilock may be available in the countries listed below.
Atenolol is reported as an ingredient of Cardilock in the following countries:
International Drug Name Search
Aténolol Zydus may be available in the countries listed below.
Atenolol is reported as an ingredient of Aténolol Zydus in the following countries:
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Solvium may be available in the countries listed below.
Ibuprofen is reported as an ingredient of Solvium in the following countries:
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Dinobroxol may be available in the countries listed below.
Ambroxol hydrochloride (a derivative of Ambroxol) is reported as an ingredient of Dinobroxol in the following countries:
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Bicalutamide Zydus France may be available in the countries listed below.
Bicalutamide is reported as an ingredient of Bicalutamide Zydus France in the following countries:
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Daga may be available in the countries listed below.
Paracetamol is reported as an ingredient of Daga in the following countries:
International Drug Name Search
In the US, Lubiprostone (lubiprostone systemic) is a member of the drug class chloride channel activators and is used to treat Constipation - Chronic and Irritable Bowel Syndrome.
US matches:
Rec.INN
A06AX03
0333963-40-9
C20-H32-F2-O5
390
Prostaglandin analogue
(-)-7-[(2R,4aR,5R,7aR)-2-(1,1-difluoropentyl)-2-hydroxy-6-oxooctahydrocyclopenta[b]pyran-5-yl]heptanoic acid (WHO)
7-[(2R,4aR,5R,7aR)-2-(1,1-difluoropentyl)-2-hydroxy-6-oxooctahydrocyclopenta[b]pyran-5-yl]heptansäure (IUPAC)
Prostan-1-oic acid, 16,16-difluoro-11-hydroxy-9,15-dioxo-, (11α)- (USAN)
International Drug Name Search
Glossary
| IUPAC | International Union of Pure and Applied Chemistry |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
| WHO | World Health Organization |
Benylin Dual Action Chesty may be available in the countries listed below.
Guaifenesin is reported as an ingredient of Benylin Dual Action Chesty in the following countries:
Pseudoephedrine hydrochloride (a derivative of Pseudoephedrine) is reported as an ingredient of Benylin Dual Action Chesty in the following countries:
International Drug Name Search
Decapeptyl Mensual may be available in the countries listed below.
Triptorelin acetate (a derivative of Triptorelin) is reported as an ingredient of Decapeptyl Mensual in the following countries:
International Drug Name Search
Algopress may be available in the countries listed below.
Mefenamic Acid is reported as an ingredient of Algopress in the following countries:
International Drug Name Search
In the US, Nipent (pentostatin systemic) is a member of the drug class antibiotics/antineoplastics and is used to treat Hairy Cell Leukemia.
US matches:
UK matches:
Pentostatin is reported as an ingredient of Nipent in the following countries:
International Drug Name Search
Glossary
| SPC | Summary of Product Characteristics (UK) |
Mikonazol CCS may be available in the countries listed below.
Miconazole nitrate (a derivative of Miconazole) is reported as an ingredient of Mikonazol CCS in the following countries:
International Drug Name Search
Procetoken may be available in the countries listed below.
Fenofibrate is reported as an ingredient of Procetoken in the following countries:
International Drug Name Search
Estelle-35 may be available in the countries listed below.
Cyproterone 17α-acetate (a derivative of Cyproterone) is reported as an ingredient of Estelle-35 in the following countries:
Ethinylestradiol is reported as an ingredient of Estelle-35 in the following countries:
International Drug Name Search
Lidocaïne Renaudin may be available in the countries listed below.
Lidocaine hydrochloride (a derivative of Lidocaine) is reported as an ingredient of Lidocaïne Renaudin in the following countries:
International Drug Name Search
Rec.INN
S01BA14
0129260-79-3
C21-H27-Cl-O5
394
Adrenal cortex hormone, glucocorticoid
Chlormethyl 11beta, 17-dihydroxy-3-oxoandrosta-1,4-dien-17beta-carboxylat (IUPAC)
Chloromethyl 11beta, 17α-dihydroxy-3-oxoandrosta-1,4-diene-17beta-carboxylate (WHO)
International Drug Name Search
Glossary
| BAN | British Approved Name |
| BANM | British Approved Name (Modified) |
| IUPAC | International Union of Pure and Applied Chemistry |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
| WHO | World Health Organization |
Metotrexato Trixilem RU may be available in the countries listed below.
Methotrexate is reported as an ingredient of Metotrexato Trixilem RU in the following countries:
International Drug Name Search
Daltrizen may be available in the countries listed below.
Dacarbazine is reported as an ingredient of Daltrizen in the following countries:
International Drug Name Search
Medapril may be available in the countries listed below.
Lisinopril is reported as an ingredient of Medapril in the following countries:
International Drug Name Search
Oxybutynin-CT may be available in the countries listed below.
Oxybutynin hydrochloride (a derivative of Oxybutynin) is reported as an ingredient of Oxybutynin-CT in the following countries:
International Drug Name Search
Fungitech may be available in the countries listed below.
Terbinafine hydrochloride (a derivative of Terbinafine) is reported as an ingredient of Fungitech in the following countries:
International Drug Name Search
Rilaquin may be available in the countries listed below.
Metoclopramide dihydrochloride (a derivative of Metoclopramide) is reported as an ingredient of Rilaquin in the following countries:
International Drug Name Search
Rec.INN
0018053-31-1
C21-H24-Cl-N3-O3
401
Analeptic
Cough suppressant
Respiratory stimulant
Benzamide, N-[3-chloro-2-[[methyl[2-(4-morpholinyl)-2-oxoethyl]amino]methyl]phenyl]-
International Drug Name Search
Glossary
| DCIT | Denominazione Comune Italiana |
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Vacontil may be available in the countries listed below.
Loperamide is reported as an ingredient of Vacontil in the following countries:
Loperamide hydrochloride (a derivative of Loperamide) is reported as an ingredient of Vacontil in the following countries:
International Drug Name Search
Azithromycin Sandoz may be available in the countries listed below.
Azithromycin is reported as an ingredient of Azithromycin Sandoz in the following countries:
Azithromycin dihydrate (a derivative of Azithromycin) is reported as an ingredient of Azithromycin Sandoz in the following countries:
Azithromycin monohydrate (a derivative of Azithromycin) is reported as an ingredient of Azithromycin Sandoz in the following countries:
Azithromycin monohydrate hemiethanolate (a derivative of Azithromycin) is reported as an ingredient of Azithromycin Sandoz in the following countries:
International Drug Name Search
0036393-20-1
C8-H12-N2-O8-Zn
329
Mineral supplement
(RS)-Zink dihydrogenaspartat (IUPAC)
International Drug Name Search
Glossary
| IUPAC | International Union of Pure and Applied Chemistry |
| IS | Inofficial Synonym |
Keramo may be available in the countries listed below.
Famotidine is reported as an ingredient of Keramo in the following countries:
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Aimafix D.I. may be available in the countries listed below.
Coagulation Factor IX, Human is reported as an ingredient of Aimafix D.I. in the following countries:
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Esorid MPS may be available in the countries listed below.
Cisapride is reported as an ingredient of Esorid MPS in the following countries:
Dimeticone is reported as an ingredient of Esorid MPS in the following countries:
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Bupicaine may be available in the countries listed below.
Bupivacaine is reported as an ingredient of Bupicaine in the following countries:
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Ranitidine Mylan may be available in the countries listed below.
Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Ranitidine Mylan in the following countries:
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Magium 5/10 Brause may be available in the countries listed below.
Magnesium Oxide light (a derivative of Magnesium Oxide) is reported as an ingredient of Magium 5/10 Brause in the following countries:
International Drug Name Search
Sterile, Preservative-Free
Restasis® (cyclosporine ophthalmic emulsion) 0.05% contains a topical immunomodulator with anti-inflammatory effects. Cyclosporine's chemical name is Cyclo[[(E) - (2S,3R,4R) - 3 - hydroxy - 4 - methyl - 2 - (methylamino) - 6 - octenoyl] - L - 2 - aminobutyryl - N - methylglycyl - N - methyl - L - leucyl - L - valyl - N - methyl - L - leucyl - L - alanyl - D - alanyl - N - methyl - L - leucyl - N - methyl - L - leucyl - N - methyl - L - valyl] and it has the following structure:
Structural Formula
Cyclosporine is a fine white powder. Restasis® appears as a white opaque to slightly translucent homogeneous emulsion. It has an osmolality of 230 to 320 mOsmol/kg and a pH of 6.5-8.0. Each mL of Restasis® ophthalmic emulsion contains: Active: cyclosporine 0.05%. Inactives: glycerin; castor oil; polysorbate 80; carbomer copolymer type A; purified water; and sodium hydroxide to adjust pH.
Cyclosporine is an immunosuppressive agent when administered systemically.
In patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca, cyclosporine emulsion is thought to act as a partial immunomodulator. The exact mechanism of action is not known.
Blood cyclosporin A concentrations were measured using a specific high pressure liquid chromatography-mass spectrometry assay. Blood concentrations of cyclosporine, in all the samples collected, after topical administration of Restasis® 0.05%, BID, in humans for up to 12 months, were below the quantitation limit of 0.1 ng/mL. There was no detectable drug accumulation in blood during 12 months of treatment with Restasis® ophthalmic emulsion.
Four multicenter, randomized, adequate and well-controlled clinical studies were performed in approximately 1200 patients with moderate to severe keratoconjunctivitis sicca. Restasis® demonstrated statistically significant increases in Schirmer wetting of 10 mm versus vehicle at six months in patients whose tear production was presumed to be suppressed due to ocular inflammation. This effect was seen in approximately 15% of Restasis® ophthalmic emulsion treated patients versus approximately 5% of vehicle treated patients. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs.
No increase in bacterial or fungal ocular infections was reported following administration of Restasis®.
Restasis® ophthalmic emulsion is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs.
Restasis® is contraindicated in patients with active ocular infections and in patients with known or suspected hypersensitivity to any of the ingredients in the formulation.
Restasis® ophthalmic emulsion has not been studied in patients with a history of herpes keratitis.
General: For ophthalmic use only.
The emulsion from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration.
Do not allow the tip of the vial to touch the eye or any surface, as this may contaminate the emulsion.
Restasis® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of Restasis® ophthalmic emulsion.
Systemic carcinogenicity studies were carried out in male and female mice and rats. In the 78-week oral (diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically significant trend was found for lymphocytic lymphomas in females, and the incidence of hepatocellular carcinomas in mid-dose males significantly exceeded the control value.
In the 24-month oral (diet) rat study, conducted at 0.5, 2, and 8 mg/kg/day, pancreatic islet cell adenomas significantly exceeded the control rate in the low dose level. The hepatocellular carcinomas and pancreatic islet cell adenomas were not dose related. The low doses in mice and rats are approximately 1000 and 500 times greater, respectively, than the daily human dose of one drop (28 μL) of 0.05% Restasis® BID into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed.
Cyclosporine has not been found mutagenic/genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay, and the DNA-repair test in sperm from treated mice. A study analyzing sister chromatid exchange (SCE) induction by cyclosporine using human lymphocytes in vitro gave indication of a positive effect (i.e., induction of SCE).
No impairment in fertility was demonstrated in studies in male and female rats receiving oral doses of cyclosporine up to 15 mg/kg/day (approximately 15,000 times the human daily dose of 0.001 mg/kg/day) for 9 weeks (male) and 2 weeks (female) prior to mating.
Pregnancy category C.
Teratogenic Effects: No evidence of teratogenicity was observed in rats or rabbits receiving oral doses of cyclosporine up to 300 mg/kg/day during organogenesis. These doses in rats and rabbits are approximately 300,000 times greater than the daily human dose of one drop (28 μL) 0.05% Restasis® BID into each eye of a 60 kg person (0.001mg/kg/day), assuming that the entire dose is absorbed.
Non-Teratogenic Effects: Adverse effects were seen in reproduction studies in rats and rabbits only at dose levels toxic to dams. At toxic doses (rats at 30 mg/kg/day and rabbits at 100 mg/kg/day), cyclosporine oral solution, USP, was embryo- and fetotoxic as indicated by increased pre- and postnatal mortality and reduced fetal weight together with related skeletal retardations. These doses are 30,000 and 100,000 times greater, respectively than the daily human dose of one drop (28 μL) of 0.05% Restasis® BID into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. No evidence of embryofetal toxicity was observed in rats or rabbits receiving cyclosporine at oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively, during organogenesis. These doses in rats and rabbits are approximately 17,000 and 30,000 times greater, respectively, than the daily human dose.
Offspring of rats receiving a 45 mg/kg/day oral dose of cyclosporine from Day 15 of pregnancy until Day 21 postpartum, a maternally toxic level, exhibited an increase in postnatal mortality; this dose is 45,000 times greater than the daily human topical dose, 0.001 mg/kg/day, assuming that the entire dose is absorbed. No adverse events were observed at oral doses up to 15 mg/kg/day (15,000 times greater than the daily human dose).
There are no adequate and well-controlled studies of Restasis® in pregnant women. Restasis® should be administered to a pregnant woman only if clearly needed.
Cyclosporine is known to be excreted in human milk following systemic administration but excretion in human milk after topical treatment has not been investigated. Although blood concentrations are undetectable after topical administration of Restasis® ophthalmic emulsion, caution should be exercised when Restasis® is administered to a nursing woman.
The safety and efficacy of Restasis® ophthalmic emulsion have not been established in pediatric patients below the age of 16.
No overall difference in safety or effectiveness has been observed between elderly and younger patients.
The most common adverse event following the use of Restasis® was ocular burning (17%).
Other events reported in 1% to 5% of patients included conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbance (most often blurring).
Invert the unit dose vial a few times to obtain a uniform, white, opaque emulsion before using. Instill one drop of Restasis® ophthalmic emulsion twice a day in each eye approximately 12 hours apart. Restasis® can be used concomitantly with artificial tears, allowing a 15 minute interval between products. Discard vial immediately after use.
Restasis® ophthalmic emulsion is packaged in single use vials. Each vial contains 0.4 mL fill in a 0.9 mL LDPE vial; 30 vials are packaged in a polypropylene tray with an aluminum peelable lid. The entire contents of each tray (30 vials) must be dispensed intact. Restasis® is also provided in a 60 count (2 x 30) package (one month supply) that must be dispensed intact.
30 Vials 0.4 mL each - NDC 0023-9163-30
60 (2 x 30) Vials 0.4 mL each - NDC 0023-9163-60
Storage: Store Restasis® ophthalmic emulsion at 15 - 25° C (59 - 77° F).
KEEP OUT OF THE REACH OF CHILDREN.
Rx Only
Revised: 02/2010
© 2010 Allergan, Inc.
Irvine, CA 92612, U.S.A.
® marks owned by Allergan, Inc.
U.S. Patent 5,474,979
Made in the U.S.A.
71876US14B
Restasis®
(cyclosporine ophthalmic emulsion) 0.05%
Allergan, Inc.
NDC 0023-9163-60
No. 93587
Restasis
(Cyclosporine Ophthalmic Emulsion) 0.05%
60 Single-Use Vials (0.4 mL each) One Month Supply Sterile, Preservative-Free
Each mL contains: Active: cyclosporine 0.05% Inactives: glycerin; castor oil; polysorbate 80; carbomer copolymer type A; purified water; and sodium hydroxide to adjust the pH. Usual Dosage: Twice daily approximately 12 hours apart. Invert the vial before using. Use immediately after opening and then discard.
Note: Store at 15 - 25° C (59 - 77° F). Store vials in the thermoformed tray until use. The entire contents of each package (60 vials) must be dispensed intact.
© 2010 Allergan, Inc.
Irvine, CA 92612, U.S.A.
® marks owned by Allergan, Inc.
U.S. Patent 5,474,979
Made in the U.S.A.
ALLERGAN
Lot:
Exp.:
Rx only
54291US13B
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NDA | NDA050790 | 04/01/2003 | |
| Labeler - Allergan, Inc. (144796497) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Allergan, Inc. | 362898611 | MANUFACTURE | |
NADA 34-879, Approved by FDA
Federal law restricts this drug to use by or on the order of a licensed veterinarian.
Doxapram hydrochloride ............................ 20 mg
Benzyl alcohol (as preservative) ................. 0.9 %
Water for Injection, USP ............................. q.s.
Dopram-V (doxapram hydrochloride) is a potent respiratory stimulant. It is unique in its ability to stimulate respiration at dosages considerably below those required to evoke cerebral cortical stimulation. In nonanesthetized animals the dose required to produce convulsions is some 70 to 75 times the dose required to produce respiratory stimulation. In anesthetized subjects, doxapram also exerts a marked arousal effect. Thus, by promoting the restoration of normal ventilation and producing early arousal following general anesthesia, doxapram minimizes or prevents the undesirable effects of post-anesthetic respiratory depression or hypoventilation and hastens recovery.
The chemical name of doxapram hydrochloride is 1-ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone hydrochloride hydrate.
The material is prepared as a clear, colorless, 2% aqueous solution with a pH of 3.5 to 5 and is stable at room temperature. Stability studies of 24 months’ duration have shown doxapram to have excellent stability characteristics. The preservative is benzyl alcohol, 0.9% and sterilization is accomplished by aseptic filtration technique. Doxapram is compatible with 5% and 10% dextrose in water or normal saline, but is physically incompatible with alkaline solutions, such as 2.5% thiopental sodium.
Species Variation2,5
The dog responds more dramatically to doxapram than other species. For example, arousal was not observed in the rat, and the cat responded poorly in comparison with the dog. Respiratory stimulation was slight in the rat, moderate in the cat and marked in the dog and horse.
Effect on EEG3
Studies show that while the drug acted selectively on respiratory centers of the brain, higher doses stimulated other parts of the neuraxis. The cortex appeared to be the most resistant part of the central nervous system to the action of the drug.
Effect on Cerebral Blood Flow4
The effect of doxapram on cerebral blood flow in anesthetized dogs was determined. Initially, the drug caused a transient increase in blood flow concomitant with rising femoral arterial blood pressure. Flow then diminished while the blood pressure remained elevated. The decreased flow appeared to coincide with marked respiratory stimulation; its occurrence, therefore, is consistent with the known vasoconstrictor effect of hypocapnia.
Effect on Pituitary-Adrenal Axis5
Intravenous administration of doxapram (20 mg/kg) to anesthetized dogs resulted in a marked rise in the adrenal venous blood level of 17-hydroxycorticosteroids. The peak response occurred at 5–7 minutes in most animals. Hypophysectomy prevented this effect of doxapram.
Site and Mechanism of Action2,3,4,7
Doxapram appeared to stimulate respirations primarily by an effect on the brain stem, since sectioning of reflex pathways did not abolish its action. The detection of increased electrical activity in both the inspiratory and expiratory centers of the medulla, at doses as low as 0.2 mg/kg, constituted confirmation of this site of action. Only after higher doses were other parts of the brain and spinal cord stimulated. Also, cross circulation experiments have shown that doxapram acts mainly through direct stimulation of central respiratory centers.
The pressor response to doxapram appears to be primarily due to stimulation of brain stem vasomotor areas and it is mediated through the sympathoadrenal system. Adrenalectomy and/or drugs which inhibit transmission at sympathetic ganglia or at sympathetic neuroeffector sites were capable of reducing the pressor response to doxapram. Spinal section at C2 abolished the pressor effect.
Intravenous infusion of doxapram to dogs resulted in a prompt and marked increase in total blood and urinary catecholamines.
Therapeutic Ratio2
Doxapram did not produce convulsions as readily as did other respiratory stimulants. In unanesthetized animals the ratios between convulsant and respiratory stimulant doses of several such drugs were as follows: doxapram, 70; ethamivan, 35; bemegride, 15; pentylenetetrazol, 4; and picrotoxin, 2.3. In animals anesthetized with barbiturates, it was not possible to establish this ratio for doxapram because convulsions could not be produced.
Interaction with Other Drugs2,5,10,11,13
The respiratory stimulant effects of doxapram in dogs were not blocked by anesthetic doses of the following: phenobarbital sodium, pentobarbital sodium, thiopental sodium, secobarbital sodium, halothane and methoxyflurane. In dogs and cats, doxapram stimulated respiration that was severely depressed with morphine or meperidine. However, convulsions occurred in cats, a species in which morphine is known to be convulsant.
The respiratory stimulant effects of doxapram in horses were not blocked by anesthetic doses of the following: chloral hydrate, chloral hydrate plus magnesium sulfate and pentobarbital sodium.
Nialamide potentiated the respiratory stimulant action of doxapram in dogs and reserpine suppressed this action. In curarized dogs, the respiratory response varied inversely with the degree of muscle relaxation existing at the time doxapram was administered.
Doxapram antagonized the depressant effects of chlorpromazine, mephenesin and methocarbamol on spinal reflexes in unanesthetized cats.
Various combinations of analeptics in acute barbiturate narcosis in dogs have been compared, including metaraminol and phenylephrine, methetharimide and amphetamine, methetharimide and phenylephrine, pentylenetetrazol and phenylephrine, pentylenetetrazol and amphetamine, doxapram and phenylephrine, and doxapram alone. While most combinations improved respiratory minute volume quickly, doxapram gave the best response of all. In a similar study comparing the effects of doxapram and various analeptic combinations in dogs, only doxapram was conspicuously effective in increasing ventilation and in shortening sleeping time.
Absorption, Distribution and Fate5,8
Respiratory stimulation was observed in the anesthetized dog after administration by the following routes: intravenous, intramuscular, intraperitoneal, oral, sublingual and subcutaneous.
Spectrophotometric methods were applied to the determination of blood levels and urinary excretion in dogs given doxapram, 10 mg/kg and 20 mg/kg, intravenously. Blood concentrations of doxapram and/or its metabolites were at peak levels immediately after injection and declined rapidly in the first hour. The concentration then further decreased slowly, and an appreciable amount was still present at the end of 24 hours. One dog was given doxapram labeled with radioactive carbon in the 2-position of the pyrrolidinone ring. Blood levels were slightly higher and urinary excretion was slightly lower by isotope assay than by chemical assay. The feces contained 29% of the administered radioactivity after 48 hours and an additional 9% in the following 24 hours.
Oral toxicity studies were carried out in nine dogs and sixty rats for 30 days. Dogs were given doxapram orally by capsule at doses of 20, 50 and 125 mg/kg/day, and one group received the drug intravenously at 20 mg/kg/day. Rats received the drug by stomach tube at 40, 80 and 160 mg/kg/day, with one group receiving 20 mg/kg intravenously daily. Four dogs died, three while receiving the high dose of 125 mg/kg and one at 50 mg/kg. At each dosage level signs of tremor, lacrimation, excessive salivation, occasional vomiting, diarrhea, stiffness of the extremities and respiratory stimulation were observed in all dogs. The hemogram, urinalysis and blood chemistry showed no changes which were considered attributable to the drug.
Histologically, the central nervous system in both species showed congestion, perivascular hemorrhages and petechial hemorrhages. These changes were interpreted as resembling hypoxic changes. The experiments were repeated in dogs at 2.5, 5, 10 and 20 mg/kg/day and no such lesions were seen.
The acute LD50 of doxapram appears to be in the same dose range for various species of animals including mice, rats, adult dogs, newborn dogs and cats. The intravenous LD50 was approximately 75 mg/kg while the oral and subcutaneous LD50’s were three to four times greater and the intraperitoneal LD50 about twice as great.
No significant irritation was produced when a saline solution of doxapram at a pH of 4.3 was administered intramuscularly to rabbits at concentrations of 1, 2 and 4%. On the other hand, aqueous solutions of the same concentrations caused tissue irritation in rabbits when given subcutaneously.
Safety Margin for the Various Species2,9
The acute LD50 of doxapram HCl in unanesthetized animals appears to be in the same dose range for various species of animals including mice, rats, adult and neonatal dogs and cats. Intravenously, the LD50 was determined to be approximately 75 mg/kg. The oral and subcutaneous LD50 was three to four times the intravenous LD50 whereas the intraperitoneal LD50 was about twice as great.2,9
The maximum tolerated dose (MTD) of doxapram HCl in unanesthetized animals appears to be in the same dose range for various species of animals including mice, rats, adult and neonatal dogs and cats. Intravenously, the highest MTD tested was determined to be approximately 40 mg/kg. The oral and subcutaneous MTD was three or four times the intravenous MTD whereas the intraperitoneal MTD was about twice as great.
The highest dose given intravenously to horses was 66 mg per 100 lbs with chloral hydrate anesthesia, and 60 mg per 100 lbs with gas anesthesia. All animals responded normally and no toxic symptoms were observed.
The clinical use of doxapram in lightly and deeply anesthetized animals has confirmed the respiratory stimulant and arousal effects previously demonstrated in the laboratory. In one study with 48 dogs and 18 cats subjected to various surgical procedures using pentobarbital sodium as the anesthetic, marked increases in ventilation occurred within one minute following a single intravenous injection of 5 mg doxapram per kg of body weight (2.5 mg/lb). The most dramatic improvement occurred in lightly anesthetized dogs pretreated with either promazine or fentanyl-droperidol and atropine. Doxapram accelerated the return of pedal reflexes in all animals.
Doxapram consistently sustained an increased heart rate beginning one minute after injection. A second injection generally failed to further increase heart rate. EKG disturbances of T-wave polarity and magnitude occurred with the use of doxapram but tended to abate with time. Second injections of doxapram generally did not aggravate the EKG distortions.
Ten animals had pre-existing EKG signs of cardiac damage and tolerated doxapram well.
In another study with 73 dogs subjected to various surgical procedures using methoxy-flurane or halothane as the anesthetic, the arousal time was materially shortened, and respiratory minute volume and rate were increased following a single intravenous injection ranging from 0.08 to 1.95 mg/lb with an average dose of 0.44 mg/lb.
Doxapram was effective in intravenous dosages of 1 mg/kg or less in increasing ventilation and reducing arousal time, especially following methoxyflurane. Tidal volume and respiratory rates were increased; the response normally occurred in 10–20 seconds following injection. No side effects were observed. There were 35 dogs under halothane and 33 dogs under methoxyflurane anesthesia in this study.
In 20 horses subjected to various surgical procedures using intravenous injections of chloral hydrate, chloral hydrate and magnesium sulfate, or pentobarbital as the anesthetic, marked increases in ventilation occurred within 30 seconds following intravenous injection of doxapram in doses ranging from 0.20 to 0.66 mg/lb with an average of 0.28 mg/lb for chloral hydrate and 0.20 to 0.25 mg/lb for the barbiturate. The arousal time was materially shortened, and respiratory minute volume and rate were increased.
In another study involving 34 horses anesthetized with halothane or methoxyflurane, marked increases in ventilation occurred within 30 seconds following intravenous injection of doxapram in doses ranging from 0.08 to 0.50 mg/lb, with an average dose of 0.21 mg/lb. The average recovery time was shortened by one-third or more.
In a series of clinical studies involving 80 neonatal canine patients, suffering respiratory crisis following dystocia or caesarean section, doxapram administered either subcutaneously, sublingually or via umbilical vein in doses from 1–5 drops (1–5 mg) resulted in a marked increase in ventilation and survival of all patients.
In a series of clinical studies involving 16 neonatal feline patients, suffering respiratory crisis following caesarean section or dystocia, doxapram administered either subcutaneously or sublingually (topically) in doses of 1 to 2 drops (1–2 mg) resulted in a marked increase in ventilation and survival of all patients.
For Dogs, Cats and Horses:
1. To stimulate respirations during and after general anesthesia.
2. To speed awakening and return of reflexes after anesthesia.
For Neonate Dogs and Cats:
1. Initiate respirations following dystocia or caesarean section.
2. To stimulate respirations following dystocia or caesarean section.
Caution: For intravenous use only in dogs, cats and horses. May be administered subcutaneously, sublingually (topically) or via umbilical vein in neonatal puppies and either subcutaneously or sublingually (topically) in neonatal kittens. Do not mix with alkaline solutions. Dopram-V (doxapram hydrochloride) is neither an antagonist of muscle relaxant drugs nor a specific narcotic antagonist.
Doses of Dopram-V should be adjusted to meet the requirements of the situation. Excessive doses may produce hyperventilation which may lead to respiratory alkalosis. A patent air passageway is essential. Adequate, but not excessive, doses should be used and the blood pressure and reflexes should be checked periodically.
DOSAGE OF Dopram-V (DOXAPRAM HYDROCHLORIDE) FOR INTRAVENOUS INJECTION | ||
| Dogs and Cats | ||
| Weight of Animal (lb) | Barbiturate Anesthesia Use 1/8 mL (2.5 mg) to ¼ mL (5 mg) per lb body weight | Gas Anesthesia Use 1/40 mL (0.5 mg) per lb body weight |
| 10 | 1¼ ml (25 mg) to 2 ½ mL (50 mg) | ¼ mL (5 mg) |
| 20 | 2 ½ mL (50 mg) to 5 mL (100 mg) | ½ mL (10 mg) |
| 30 | 3¾ mL (75 mg) to 7½ mL (150 mg) | ¾ mL (15 mg) |
| 50 | 6¼ mL (125 mg) to 12½ mL (250 mg) | 1 ¼ mL (25 mg) |
| Dosage should be adjusted for depth of anesthesia, respiratory volume and rate. Dosage can be repeated in 15 to 20 minutes, if necessary. | ||
| Horses | ||
| Weight of Animal (lb) | Chloral hydrate, chloral hydrate and magnesium sulfate barbiturates, use 0.0125 mL (0.25 mg) per lb body weight | Inhalation anesthesia halothane, methoxyflurane use 0.01 mL (0.20 mg) per lb body weight |
| 100 | 1 ¼ mL (25 mg) | 1 mL (20 mg) |
| 200 | 2 ½ mL (50 mg) | 2 mL (40 mg) |
| 500 | 6 ¼ mL (125 mg) | 5 ml (100 mg) |
| 1000 | 12 ½ mL (250 mg) | 10 mL (200 mg) |
DOSAGE OF Dopram-V (DOXAPRAM HYDROCHLORIDE) FOR NEONATE USE
Neonate Canine
Doxapram may be administered either subcutaneously, sublingually (topically) or via the umbilical vein in doses of 1 - 5 drops (1 - 5 mg) depending on size of neonate and degree of respiratory crisis.
Technique for Umbilical Vein Administration
When the neonate is presented through the incision of the uterus, placental membrane and fluid are removed from mouth and nose. A clamp is placed across the umbilical cord approximately 1-2 inches from abdomen of neonate. The umbilical vein is isolated and the selected dose of doxapram injected directly into the umbilical vein.
Neonate Feline
Doxapram may be adminstered either subcutaneously or sublingually (topically) in a dose of 1 - 2 drops (1 - 2 mg) depending on severity of respiratory crisis.
The action of Dopram-V (doxapram hydrochloride) is rapid, usually beginning in a few seconds. The duration and intensity of response depends upon the dose, the condition of the animal at the time the drug is administered, and depth of anesthesia. Repeated doses should not be given until the effects of the first dose have passed and the condition of the patient requires it.
Dosage should be adjusted for depth of anesthesia, respiratory volume and rate. Dosage can be repeated in 15 to 20 minutes, if necessary.
Note: Vial should be discarded after a maximum of 50 entries.
Dopram-V (doxapram hydrochloride) is available in 20 mL multiple dose vials of the sterile solution.
NDC 0010-4701-01 - 20 mL multiple dose vial - 20 mg/mL
Store at controlled room temperature 15 - 30°C (59 - 86°F).
1. Lunsford, C.; Cale, Jr., A. D.; Ward, J. W.; Franko, B. V. and Jenkins, H.: 4-(b-substituted ethyl)-3, 3-diphenyl-2-pyrrolidinones. A new series of CNS stimulants. J. Med. Chem. 7:302 (1964).
2. Ward, J. W. and Franko, B. V.: A New Centrally Acting Agent (AHR-619) with Marked Respiratory Stimulating, Pressor, and “Awakening’’ Effects; Fed. Proc. 27:(2):325 (1962).
3. Funderburk, W. H.; Oliver, K. L. and Ward, J. W.: Electrophysiologic Analysis of the Site of Action of Doxapram Hydrochloride. J. Pharmacol. Exp. Ther. 151:3 (1966).
4. Funderburk, W. H.; Oliver, K. L.; Ward, J. W.: Cerebral Blood Flow Changes Due to Doxapram Hydrochloride (AHR-619); Fed. Proc. 22:(2):482 (Abstract) (1963).
5. Reports on File. Pharmacology Department, A. H. Robins Company.
6. Alphin, R. S. and Franko, B. V.: Inhibition and Stimulation of Gastric Secretions by Doxapram Hydrochloride (AHR-619); Fed. Proc. 22(2):662 (Abstract) (1963).
7. Kato, H. and Buckley, J. P.: Possible Sites of Action of the Respiratory Stimulant Effects of Doxapram Hydrochloride. J. Pharmacol. Exp. Ther. 144:260 (1964).
8. Bruce, R. B.; Pitts, J. E.; Pinchbeck, F. and Newman, J.: Excretion, Distribution, and Metabolism of Doxapram Hydrochloride. J. of Med. Chem. 8:157 (1965).
9. Woodard, G.; Ward, J. W. and Mann, G. T.: Safety Evaluation of the Respiratory Stimulant Doxapram Hydrochloride by Oral and Parenteral Administration to Laboratory Animals. Tox. and Appl. Pharmacol. 6:364 (1964).
10. Klemm, W. R.: Physiologic Responses to Equivalent Doses of Doxapram and Various Analeptic Combinations in Acute Barbiturate Narcosis in Dogs. Tox. and Appl. Pharmacol. 8:505 (1966).
11. Klemm, W. R.: Evaluation of Effectiveness of Doxapram and Various Analeptic Combinations in Dogs. J. Am. Vet. Med. Assoc. 148:894 (1966).
12. Jensen, E. C. and Klemm, W. R.: Clinical Evaluation of an Analeptic, Doxapram, in Dogs and Cats. J. Am. Vet. Med. Assoc. 150(5):516–525 (1967).
13. Polak, A. and Plum, F.: Comparison of New Analeptics in Barbiturate-Poisoned Animals. J. Pharmacol. Exp. Ther. 145:27 (1964).
14. Short, C. E.: Proc. American Animal Hospital Association, Washington, D. C., 1969.
Dopram is a registered trademark of Baxter Healthcare Corporation and is used under license.
© 2010 Boehringer Ingelheim Vetmedica, Inc. All Rights Reserved.
Manufactured for:
Boehringer Ingelheim Vetmedica, Inc.
St. Joseph, MO 64506 U.S.A.
11960 Rev. July 2010 5020H P688-298USA/01-10
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NADA | NADA034879 | 05/02/1967 | |
| Labeler - Boehringer Ingelheim Vetmedica, Inc. (007134091) |
| Registrant - Boehringer Ingelheim Vetmedica, Inc. (007134091) |
