Fexofenadin-Sandoz may be available in the countries listed below.
Fexofenadine hydrochloride (a derivative of Fexofenadine) is reported as an ingredient of Fexofenadin-Sandoz in the following countries:
International Drug Name Search
Generic Name: diphenhydramine (DYE fen HYE dra meen)
Brand Names: Aler-Tab, Allergy, Allermax, Altaryl, Benadryl Allergy, Benadryl DF, Benadryl Dye Free Allergy, Benadryl Ultratab, Children's Allergy, Diphen Cough, Diphenhist, Dytuss, PediaCare Children's Allergy, Q-Dryl, Q-Dryl A/F, Siladryl, Siladryl Allergy, Silphen Cough, Simply Sleep, Sleep-ettes, Sleep-ettes D, Sominex Maximum Strength Caplet, Theraflu Thin Strips Multi Symptom, Triaminic Thin Strips Cough & Runny Nose, Unisom Sleepgels Maximum Strength, Valu-Dryl
Diphenhydramine is an antihistamine. Diphenhydramine blocks the effects of the naturally occurring chemical histamine in the body.
Diphenhydramine is used to treat sneezing; runny nose; itching, watery eyes; hives; rashes; itching; and other symptoms of allergies and the common cold.
Diphenhydramine is also used to suppress coughs, to treat motion sickness, to induce sleep, and to treat mild forms of Parkinson's disease.
Diphenhydramine may also be used for purposes other than those listed in this medication guide.
Before taking this medication, tell your doctor if you have
glaucoma or increased pressure in the eye;
a stomach ulcer;
an enlarged prostate, bladder problems or difficulty urinating;
an overactive thyroid (hyperthyroidism);
hypertension or any type of heart problems; or
asthma.
You may not be able to take diphenhydramine, or you may require a lower dose or special monitoring during treatment if you have any of the conditions listed above.
Take diphenhydramine exactly as directed on the package or as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.
Diphenhydramine can be taken with or without food.
For motion sickness, a dose is usually taken 30 minutes before motion, then with meals and at bedtime for the duration of exposure.
As a sleep aid, diphenhydramine should be taken approximately 30 minutes before bedtime.
To ensure that you get a correct dose, measure the liquid forms of diphenhydramine with a special dose-measuring spoon or cup, not with a regular tablespoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.
Never take more of this medication than is prescribed for you. The maximum amount of diphenhydramine that you should take in any 24-hour period is 300 mg.
Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.
Symptoms of a diphenhydramine overdose include extreme sleepiness, confusion, weakness, ringing in the ears, blurred vision, large pupils, dry mouth, flushing, fever, shaking, insomnia, hallucinations, and possibly seizures.
Other, less serious side effects may be more likely to occur. Continue to take diphenhydramine and talk to your doctor if you experience
sleepiness, fatigue, or dizziness;
headache;
dry mouth; or
difficulty urinating or an enlarged prostate.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Talk to your pharmacist before taking other over-the-counter cough, cold, allergy, or insomnia medications. These products may contain medicines similar to diphenhydramine, which could lead to an antihistamine overdose.
Before taking this medication, tell your doctor if you are taking any of the following medicines:
anxiety or sleep medicines such as alprazolam (Xanax), diazepam (Valium), chlordiazepoxide (Librium), temazepam (Restoril), or triazolam (Halcion);
medications for depression such as amitriptyline (Elavil), doxepin (Sinequan), nortriptyline (Pamelor), fluoxetine (Prozac), sertraline (Zoloft), or paroxetine (Paxil); or
any other medications that make you feel drowsy, sleepy, or relaxed.
Drugs other than those listed here may also interact with diphenhydramine. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.
See also: Sleep side effects (in more detail)
Drossadinetten may be available in the countries listed below.
Lactic Acid aluminium (a derivative of Lactic Acid) is reported as an ingredient of Drossadinetten in the following countries:
Lidocaine hydrochloride (a derivative of Lidocaine) is reported as an ingredient of Drossadinetten in the following countries:
International Drug Name Search
(6% Salicylic Acid)
Rx only
FOR DERMATOLOGICAL USE ONLY.
NOT FOR OPHTHALMIC, ORAL OR INTRAVAGINAL USE.
SALACYN™ 6% CREAM contains 6% Salicyclic Acid USP incorporated into a specially formulated oil and water emulsion vehicle consisting of Ammonium Lactate, Cetearyl Alcohol and PEG-3 Distearoylamidoethylmonium Methosulfate and Polysorbate 60, Cetearyl Alcohol, Cetyl Alcohol, Dimethicone 350, Disodium EDTA, Glycerin, Glyceryl Stearate SE, Methylparaben, Mineral Oil, PEG-100 Stearate, Phenoxyethanol, Propylparaben, Purified Water and Trolamine.
SALACYN™ 6% LOTION contains 6% w/w Salicylic Acid USP incorporated into a specially formulated oil and water emulsion vehicle consisting of of Ammonium Lactate, Cetearyl Alcohol and PEG-3 Distearoylamidoethylmonium Methosulfate and Polysorbate 60, Cetyl Alcohol, Dimethicone 350, Disodium EDTA, Glycerin, Glyceryl Stearate SE, Methylparben, Mineral Oil, PEG-100 Stearate, Propylparaben, Purified Water and Trolamine.
Salicylic Acid is the 2-hydroxy derivative of benzoic acid having the following structure:
Salicylic Acid has been shown to produce desquamation of the horny layer of the skin while not effecting qualitative or quantitative changes in the structure of the viable epidermis. The mechanism of action has been attributed to a dissolution of intercellular cement substance. In a study of the percutaneous absorption of salicylic acid in a 6% salicylic acid gel in four patients with extensive active psoriasis. Taylor and Halprin showed that the peak serum salicylate levels never exceeded 5 mg/100 ml even though more than 60% of the applied salicylic acid was absorbed. Systemic toxic reactions are usually associated with much higher serum levels (30 to 40 mg/100ml). Peak serum levels occurred within five hours of the topical application under occlusion. The sites were occluded for 10 hours over the entire body surface below the neck. Since salicylates are distributed in the extracellular space, patients with a contracted excellular space due to dehydration or diuretics have higher salicylate levels than those with a normal extracellular space. (SEE PRECAUTIONS).
The major metabolites identified in the urine after topical administration are salicyluric acid (52%), salicylate glucuronides (42%) and free salicylic acid (6%). The urinary metabolites after percutaneous absorption differ from those after oral salicylate administration; those derived from percutaneous absorption contain more salicylate glucuronides and less salicyluric and salicylic acid. Almost 95% of a single dose of salicylate is excreted within 24 hours of its entrance into the extracellular space.
Fifty to eighty percent of salicylate is protein bound to albumin. Salicylates compete with the binding of several drugs and can modify the action of these drugs; by similar competitive mechanisms other drugs can influence the serum levels of salicylate. (SEE PRECAUTIONS).
SALACYN™ 6% is a topical aid in the removal of excessive keratin in hyperkeratotic skin disorders including verrucae, and the various ichthyoses (vulgaris, sex-linked and lamellar), keratosis palmaris and plantaris keratosis pilaris, pityriasis rubra pilaris and psoriasis (including body, scalp, palms and soles).
SALACYN™ 6% is a topical aid in the removal of excessive keratin on dorsal and plantar hyperkeratotic lesions. Topical preparations of 6% salicylic acid have been reported to be useful adjunctive therapy for verrucae plantares.
SALACYN™ 6% should not be used in any patient known to be sensitive to salicylic acid or any other listed ingredients. SALACYN™ 6% should not be used in children under 2 years of age.
Prolonged and repeated daily use over large areas, especially in children and those patients with significant renal or hepatic impariment could result in salicylism. Concomitant use of other drugs which may contribute to elevated serum salucylate levels should be avoided where the potential for toxicity is present. In children under 12 years of age and those patients with renal of hepatic impairment to the area to be treated should be limited and the patient monitored closely for signs of salicylate toxicity; nausea, vomiting, dizziness, loss of hearing, tinnitus, lethargy, hyperpnea, diarrhea, and psychic disturbances. In the event of salicylic acid toxicity, the use of SALACYN™ 6% should be discontinued. Fluids should be administered to promote urinary execration. Treatment with sodium bicarbonate (oral or intravenous) should be instituted as appropriate. Patients should be cautioned against the use of oral aspirin and other salicylate containing medications, such as sports injury creams, to avoid additional excessive exposure to salicylic acid. Where needed, aspirin should be replaced by an alternative non-steroidal anti-inflammatory agent that is not salicylate based. Patients should be advised not to apply occlusive dressings, clothing or other occlusive topical products such as petrolatum-based ointments to prevent excessive systemic exposure to salicylic acid. Excessive application of the product other than is needed to cover the affected area will not result in a more rapid therapeutic benefit.
Due to the potential risk of developing Reye's syndrome, salicylate products should not be used in children and teenagers with varicella or influenza, unless directed by a physician.
For external use only. Avoid contact with eyes and other mucous membranes.
The following interactions are from a published review and include reports concerning both oral and topical salicylate administration. The relationship of these interactions to the use of SALACYN™ 6% is not known.
| DRUG | DISCRIPTION OF INTERACTION |
|---|---|
| Sulfonylureas | Hypoglycemia potentiated |
| Methotrexate | Decreases tubular reabsorption; clinical toxicity from methotrexate can result. |
| Oral Anticoagulants | Increased bleeding |
| DRUG | DISCRIPTION OF INTERACTION |
|---|---|
| Corticosteroids | Decreases plasma salicylate level; tapering doses of steroids may promote salicylism. |
| Acidifying agents | Increases plasma salicylate levels. |
| Alkcanizing agents | Decreased plasma salicylate levels. |
| DRUG | DISCRIPTION OF INTERACTION |
|---|---|
| Heparin | Salicylate decreases platelet adhesiveness and inteferes with hemostasis in heparin treated patients. |
| Pyrazinamide | Inhibits pyrazinamide induced hyperuricemia. |
| Uricosuric Agents | Effect of probenemide, sulfinpyrazone and phenylbutazone inhibited. |
The following alterations of laboratory tests have been reported during salicylate therapy:
| LABORATORY TESTS | EFFECT OF SALICYLATES |
|---|---|
| Thyroid Function | Decreased PBI; increased T3 uptake. |
| Urinary Sugar | False negative with glucose oxidase; false positive with Clinitest with high-dose salicylate therapy (2-5g q.d.). |
| 5-Hydroxyindole acetic acid | False negative with fluorometric test. |
| Acetone, ketone bodies | False positive FeCl3 in Gerhardt reaction; red color persist with boiling. |
| 17-OH corticosteroids | False reduced values with >4.8g. q.d. salicylate. |
| Vanilmandelic acid | False reduced values. |
| Uric acid | May increase or decrease depending on dose. |
| Prothrombin | Decreased levels; slightly increased prothrombin time. |
Salicylic acid has been shown to be teratogenic in rats and monkeys. It is difficult to extrapolate from oral doses of acetylsalicylic acid used in these studies to topical administration as the oral does to monkeys may represent six times the maximal daily human does of salicylic acid when applied topically over a large body surface. There are no adequate and well-controlled studies in pregnant women. SALACYN™ 6% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Because of the potential for serious adverse reactions in nursing infants from the mother's use of SALACYN™ 6%, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. If used by nursing mothers, it should not be used on the chest area to avoid accidental contamination of the child.
No data are available concerning potential carcinogenic or reproductive effects of SALACYN™ 6%. It has been shown to lack mutagenic potential in the Ames Salmonella test.
Excessive erythema and scaling conceivably could result from the use on open skin lesions.
SEE WARNINGS.
The preferable method of use is to apply SALACYN™ 6% thoroughly to the affected area and to cover the treated area at night after washing and before retiring. Preferably, the skin should be hydrated for at least five minutes prior to application. The medication is washed off in the morning and if excessive drying and/or irritation is observed, a bland cream or lotion may be applied. Once clearing is apparent, the occasional use of SALACYN™ 6% will usually maintain the remission. In those areas where occulsion is difficult or impossible, application may be made more frequently; hydration by wet packs or baths prior to application apparently enhances the effect. (SEE WARNINGS). Unless hands are being treated, hands should be rinsed thoroughly after application. Excessive repeated application of SALACYN™ 6% will not necessarily increase its therapeutic benefit, but could result in increased local intolerance and systemic adverse effects such as salicylism.
SALACYN™ 6% CREAM is available in 400 gram bottles, NDC 58980-631-90.
SALACYN™ 6% LOTION is available in 14 fl oz (414ml) bottles, NDC 58980-630-14
Store at controlled room temperature 20° - 25°C (68° - 77°F). Do not freeze.
Distributed by
STRATUS
PHARMACEUTICALS INC
Manufactured by
Sonar Products Inc.
Carlstadt, NJ 07072
exclusively for
Stratus Pharmaceuticals Inc.
12379 Southwest 130th Street
Miami, Florida 33186-6208
Customer Service
Telephone: 1-800-442-7882
Fax: 305-254-6875
©2008 Stratus Pharmaceuticals Inc.
SA6-IN200812.
NDC 58980-631-90
Rx only
SALACYN
CREAM
(6% Salicylic Acid)
STRATUS
PHARMACEUTICALS INC
Net WT. 400 grams
NDC 58980-630-14
Rx only
SALACYN
LOTION
(6% Salicylic Acid)
STRATUS
PHARMACEUTICALS INC
Net WT. 14.0 fl. oz. (414 mL)
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| UNAPPROVED DRUG OTHER | 03/23/2009 | ||
| SALACYN salicylic acid lotion | ||||||||||||||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| UNAPPROVED DRUG OTHER | 03/23/2009 | ||
| Labeler - Stratus Pharamceuticals, Inc (789001641) |
| Registrant - Sonar Products, Inc (104283945) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Sonar Products, Inc | 104283945 | MANUFACTURE | |
Generic Name: sulfacetamide ophthalmic (SUL fa SEET a mide off THAL mik)
Brand Names: Bleph-10, Ocu-Sul 10, Ocu-Sul 15, Ocu-Sul 30, Sodium Sulamyd, Sulf-10, Sulfac 10%
Sulfacetamide ophthalmic is an antibiotic.
Sulfacetamide ophthalmic is used to treat bacterial infections of the eyes.
Sulfacetamide ophthalmic may also be used for purposes other than those listed in this medication guide.
Apply light pressure to the inside corner of your eye (near your nose) after each drop to prevent the fluid from draining down your tear ducts.
Do not use sulfacetamide ophthalmic if you have ever had an allergic reaction to a sulfa-based drug.
Use sulfacetamide ophthalmic eyedrops or ointment exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.
To apply the eye drops:
Shake the drops gently to be sure the medicine is well mixed. Tilt your head back slightly and pull down on your lower eyelid. Position the dropper above your eye. Look up and away from the dropper. Squeeze out a drop and close your eye. Apply gentle pressure to the inside corner of your eye (near your nose) for about 1 minute to prevent the liquid from draining down your tear duct. If you are using more than one drop in the same eye or drops in both eyes, repeat the process with about 5 minutes between drops.
To apply the ointment:
Hold the tube in your hand for a few minutes to warm it up so that the ointment comes out easily. Tilt your head back slightly and pull down gently on your lower eyelid. Apply a thin film of the ointment into your lower eyelid. Close your eye and roll your eyeball around in all directions for 1 to 2 minutes. If you are applying another eye medication, allow at least 10 minutes before the next application.
Apply the missed dose as soon as you remember. However, if it is almost time for your next regularly scheduled dose, skip the missed dose and apply the next one as directed. Do not use a double dose of this medication.
An overdose of this medication is unlikely to occur. If you do suspect an overdose, wash the eye with water and call an emergency room or poison control center near you. If the drops or ointment have been ingested, drink plenty of fluid and call an emergency center for advice.
If you wear contact lenses, ask your doctor if you should wear them during treatment with sulfacetamide ophthalmic. After applying the medication, wait at least 15 minutes before inserting contact lenses, unless otherwise directed by your doctor.
Serious side effects are not expected with this medication.
Commonly, some eye burning, stinging, irritation, itching, redness, blurred vision, eyelid itching, eyelid swelling, or sensitivity to light may occur.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Do not use this medication with other eyedrops containing nitrates (e.g., silver nitrate).
Drugs other than those listed here may also interact with sulfacetamide ophthalmic. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.
See also: Sulfacet Sodium side effects (in more detail)
Furosémide EG may be available in the countries listed below.
Furosemide is reported as an ingredient of Furosémide EG in the following countries:
International Drug Name Search
P-20 may be available in the countries listed below.
Pantoprazole is reported as an ingredient of P-20 in the following countries:
International Drug Name Search
Treating acne. It may also be used for other conditions as determined by your doctor.
Sulfacetamide Suspension is a sulfonamide antibiotic. It works by killing sensitive bacteria.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Sulfacetamide Suspension. 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 Sulfacetamide Suspension. Because little, if any, of Sulfacetamide Suspension is absorbed into the blood, the risks of it interacting with another medicine is low.
Ask your health care provider if Sulfacetamide Suspension 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 Sulfacetamide Suspension 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 Sulfacetamide Suspension.
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:
Mild reddening or scaling of the skin.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); fever, chills, or persistent sore throat; severe or persistent irritation; swollen, blistered, or peeling skin; unusual tiredness or weakness; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Sulfacetamide Suspension may be harmful if swallowed.
Store Sulfacetamide Suspension at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), in a tightly closed container. Store away from heath, moisture, and light. Keep Sulfacetamide Suspension out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Sulfacetamide Suspension. 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.
Clopidogrel hydrochlorid Hexal may be available in the countries listed below.
Clopidogrel hydrochloride (a derivative of Clopidogrel) is reported as an ingredient of Clopidogrel hydrochlorid Hexal in the following countries:
International Drug Name Search
Lamotren may be available in the countries listed below.
Lamotrigine is reported as an ingredient of Lamotren in the following countries:
International Drug Name Search
Metoprolol Tartrate Injection, USP, is a selective beta 1-adrenoreceptor blocking agent, available as 5 mL single dose vials for intravenous administration. Each vial contains a sterile solution of Metoprolol Tartrate, USP, 5 mg, Sodium Chloride, USP, 45 mg, and Water for Injection, USP. Metoprolol tartrate is (±)-1-(Isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol L-(+)-tartrate (2:1) salt, and its structural formula is:
Molecular Formula: (C15H25NO3)2•C4H6O6
Metoprolol Tartrate, USP is a white, practically odorless, crystalline powder with a molecular weight of 684.82. It is very soluble in water; freely soluble in methylene chloride, in chloroform, and in alcohol; slightly soluble in acetone; and insoluble in ether.
Metoprolol is a beta-adrenergic receptor blocking agent. In vitro and in vivo animal studies have shown that it has a preferential effect on beta1 adrenoreceptors, chiefly located in cardiac muscle. This preferential effect is not absolute, however, and at higher doses, metoprolol also inhibits beta2 adrenoreceptors, chiefly located in the bronchial and vascular musculature.
Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia.
Relative beta1 selectivity has been confirmed by the following: (1) In normal subjects, metoprolol is unable to reverse the beta 2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective (beta1 plus beta2) beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, metoprolol reduces FEV1 and FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta1-receptor blocking doses.
Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at doses much greater than required for beta-blockade. Metoprolol crosses the blood-brain barrier and has been reported in the CSF in a concentration 78% of the simultaneous plasma concentration. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction.
In controlled clinical studies, metoprolol has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics, at dosages of 100 - 450 mg daily. In controlled, comparative, clinical studies, metoprolol has been shown to be as effective an antihypertensive agent as propranolol, methyldopa, and thiazide-type diuretics, and to be equally effective in supine and standing positions.
The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity.
By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris. However, in patients with heart failure, beta-adrenergic blockade may increase oxygen requirements by increasing left ventricular fiber length and end-diastolic pressure.
Although beta-adrenergic receptor blockade is useful in the treatment of angina and hypertension, there are situations in which sympathetic stimulation is vital. In patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. In the presence of AV block, beta-blockade may prevent the necessary facilitating effect of sympathetic activity on conduction. Beta2-adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients.
In controlled clinical trials, metoprolol administered two or four times daily, has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance. The dosage used in these studies ranged from 100 - 400 mg daily. A controlled, comparative, clinical trial showed that metoprolol was indistinguishable from propranolol in the treatment of angina pectoris.
In a large (1,395 patients randomized), double-blind, placebo-controlled clinical study, metoprolol was shown to reduce 3-month mortality by 36% in patients with suspected or definite myocardial infarction.
Patients were randomized and treated as soon as possible after their arrival in the hospital, once their clinical condition had stabilized and their hemodynamic status had been carefully evaluated. Subjects were ineligible if they had hypotension, bradycardia, peripheral signs of shock, and/or more than minimal basal rales as signs of congestive heart failure. Initial treatment consisted of intravenous followed by oral administration of metoprolol or placebo, given in a coronary care or comparable unit. Oral maintenance therapy with metoprolol or placebo was then continued for 3 months. After this double-blind period, all patients were given metoprolol and followed up to 1 year.
The median delay from the onset of symptoms to the initiation of therapy was 8 hours in both the metoprolol- and placebo-treatment groups. Among patients treated with metoprolol, there were comparable reductions in 3-month mortality for those treated early (≤ 8 hours) and those in whom treatment was started later. Significant reductions in the incidence of ventricular fibrillation and in chest pain following initial intravenous therapy were also observed with metoprolol and were independent of the interval between onset of symptoms and initiation of therapy.
The precise mechanism of action of metoprolol in patients with suspected or definite myocardial infarction is not known.
In this study, patients treated with metoprolol received the drug both very early (intravenously) and during a subsequent 3-month period, while placebo patients received no beta-blocker treatment for this period. The study thus was able to show a benefit from the overall metoprolol regimen but cannot separate the benefit of very early intravenous treatment from the benefit of later beta-blocker therapy. Nonetheless, because the overall regimen showed a clear beneficial effect on survival without evidence of an early adverse effect on survival, one acceptable dosage regimen is the precise regimen used in the trial. Because the specific benefit of very early treatment remains to be defined however, it is also reasonable to administer the drug orally to patients at a later time as is recommended for certain other beta-blockers.
Metoprolol is a beta-adrenergic receptor blocking agent. In vitro and in vivo animal studies have shown that it has a preferential effect on beta1 adrenoreceptors, chiefly located in cardiac muscle. This preferential effect is not absolute, however, and at higher doses, metoprolol also inhibits beta2 adrenoreceptors, chiefly located in the bronchial and vascular musculature.
Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia.
Relative beta1 selectivity has been confirmed by the following: (1) In normal subjects, metoprolol is unable to reverse the beta2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective (beta1 plus beta2) beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, metoprolol reduces FEV1 and FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta1-receptor blocking doses.
Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at doses much greater than required for beta blockade. Metoprolol crosses the blood-brain barrier and has been reported in the CSF in a concentration 78% of the simultaneous plasma concentration. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction.
In controlled clinical studies, metoprolol has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics, at dosages of 100-450 mg daily. In controlled, comparative, clinical studies, metoprolol has been shown to be as effective an antihypertensive agent as propranolol, methyldopa, and thiazide-type diuretics, and to be equally effective in supine and standing positions.
The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity.
By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris. However, in patients with heart failure, beta-adrenergic blockade may increase oxygen requirements by increasing left ventricular fiber length and end-diastolic pressure.
Although beta-adrenergic receptor blockade is useful in the treatment of angina and hypertension, there are situations in which sympathetic stimulation is vital. In patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. In the presence of AV block, beta-blockade may prevent the necessary facilitating effect of sympathetic activity on conduction. Beta2-adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients.
In controlled clinical trials, metoprolol administered two or four times daily, has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance. The dosage used in these studies ranged from 100-400 mg daily. A controlled, comparative, clinical trial showed that metoprolol was indistinguishable from propranolol in the treatment of angina pectoris.
In a large (1,395 patients randomized), double-blind, placebo-controlled clinical study, metoprolol was shown to reduce 3-month mortality by 36% in patients with suspected or definite myocardial infarction.
Patients were randomized and treated as soon as possible after their arrival in the hospital, once their clinical condition had stabilized and their hemodynamic status had been carefully evaluated. Subjects were ineligible if they had hypotension, bradycardia, peripheral signs of shock, and/or more than minimal basal rales as signs of congestive heart failure. Initial treatment consisted of intravenous followed by oral administration of metoprolol or placebo, given in a coronary care or comparable unit. Oral maintenance therapy with metoprolol or placebo was then continued for 3 months. After this double-blind period, all patients were given metoprolol and followed up to 1 year.
The median delay from the onset of symptoms to the initiation of therapy was 8 hours in both the metoprolol- and placebo-treatment groups. Among patients treated with metoprolol, there were comparable reductions in 3-month mortality for those treated early (≤8 hours) and those in whom treatment was started later. Significant reductions in the incidence of ventricular fibrillation and in chest pain following initial intravenous therapy were also observed with metoprolol and were independent of the interval between onset of symptoms and initiation of therapy.
The precise mechanism of action of metoprolol in patients with suspected or definite myocardial infarction is not known.
In this study, patients treated with metoprolol received the drug both very early (intravenously) and during a subsequent 3-month period, while placebo patients received no beta-blocker treatment for this period. The study thus was able to show a benefit from the overall metoprolol regimen but cannot separate the benefit of very early intravenous treatment from the benefit of later beta-blocker therapy. Nonetheless, because the overall regimen showed a clear beneficial effect on survival without evidence of an early adverse effect on survival, one acceptable dosage regimen is the precise regimen used in the trial. Because the specific benefit of very early treatment remains to be defined however, it is also reasonable to administer the drug orally to patients at a later time as is recommended for certain other beta-blockers.
In man, absorption of metoprolol is rapid and complete. Plasma levels following oral administration, however, approximate 50% of levels following intravenous administration, indicating about 50% first-pass metabolism.
Plasma levels achieved are highly variable after oral administration. Only a small fraction of the drug (about 12%) is bound to human serum albumin. Metoprolol is a racemic mixture of R- and S-enantiomers. Elimination is mainly by biotransformation in the liver, and the plasma half-life ranges from approximately 3 to 7 hours. The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. Consequently, no reduction in dosage is usually needed in patients with chronic renal failure.
Metoprolol is extensively metabolized by the cytochrome P450 enzyme system in the liver. The oxidative metabolism of metoprolol is under genetic control with a major contribution of the polymorphic cytochrome P450 isoform 2D6 (CYP2D6). There are marked ethnic differences in the prevalence of the poor metabolizers (PM) phenotype. Approximately 7% of Caucasians and less than 1% Orientals are poor metabolizers.
Poor CYP2D6 metabolizers exhibit several-fold higher plasma concentrations of metoprolol than extensive metabolizers with normal CYP2D6 activity. The elimination half-life of metoprolol is about 7.5 hours in poor metabolizers and 2.8 hours in extensive metabolizers. However, the CYP2D6 dependent metabolism of metoprolol seems to have little or no effect on safety or tolerability of the drug. None of the metabolites of metoprolol contribute significantly to its beta-blocking effect.
Significant beta-blocking effect (as measured by reduction of exercise heart rate) occurs within 1 hour after oral administration, and its duration is dose-related. For example, a 50% reduction of the maximum registered effect after single oral doses of 20, 50, and 100 mg occurred at 3.3, 5.0, and 6.4 hours, respectively, in normal subjects. After repeated oral dosages of 100 mg twice daily, a significant reduction in exercise systolic blood pressure was evident at 12 hours.
Following intravenous administration of metoprolol, the urinary recovery of unchanged drug is approximately 10%. When the drug was infused over a 10-minute period, in normal volunteers, maximum beta-blockade was achieved at approximately 20 minutes. Doses of 5 mg and 15 mg yielded a maximal reduction in exercise-induced heart rate of approximately 10% and 15%, respectively. The effect on exercise heart rate decreased linearly with time at the same rate for both doses, and disappeared at approximately 5 hours and 8 hours for the 5 mg and 15 mg doses, respectively.
Equivalent maximal beta-blocking effect is achieved with oral and intravenous doses in the ratio of approximately 2.5:1.
There is a linear relationship between the log of plasma levels and reduction of exercise heart rate. However, antihypertensive activity does not appear to be related to plasma levels. Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihypertensive activity to dose, selection of proper dosage requires individual titration.
In several studies of patients with acute myocardial infarction, intravenous followed by oral administration of metoprolol caused a reduction in heart rate, systolic blood pressure, and cardiac output. Stroke volume, diastolic blood pressure, and pulmonary artery end diastolic pressure remained unchanged.
In patients with angina pectoris, plasma concentration measured at 1 hour is linearly related to the oral dose within the range of 50 - 400 mg. Exercise heart rate and systolic blood pressure are reduced in relation to the logarithm of the oral dose of metoprolol. The increase in exercise capacity and the reduction in left ventricular ischemia are also significantly related to the logarithm of the oral dose.
In elderly subjects with clinically normal renal and hepatic function, there are no significant differences in metoprolol pharmacokinetics compared to young subjects
Metoprolol Tartrate Injection, USP is indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment with intravenous Metoprolol Tartrate Injection, USP can be initiated as soon as the patient’s clinical condition allows (see DOSAGE AND ADMINISTRATION , CONTRAINDICATIONS , and WARNINGS ). Alternatively, treatment can begin within 3 to 10 days of the acute event (see DOSAGE AND ADMINISTRATION ).
Metoprolol is contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure (see WARNINGS ).
Hypersensitivity to metoprolol and related derivatives, or to any of the excipients; hypersensitivity to other beta-blockers (cross sensitivity between beta-blockers can occur).
Sick-sinus syndrome.
Severe peripheral arterial circulatory disorders
Metoprolol is contraindicated in patients with a heart rate < 45 beats/min; second- and third-degree heart block; significant first-degree heart block (P-R interval ≥ 0.24 sec); systolic blood pressure < 100 mmHg; or moderate-to-severe cardiac failure (see WARNINGS ).
Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure, and beta-blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In hypertensive and angina patients who have congestive heart failure controlled by digitalis and diuretics, metoprolol should be administered cautiously.
In Patients Without a History of Cardiac Failure:Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or given a diuretic. The response should be observed closely. If cardiac failure continues, despite adequate digitalization and diuretic therapy, metoprolol should be withdrawn.
Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS, including metoproplol. Because of its relative beta1 selectivity, however, metoprolol may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since beta1 selectivity is not absolute, a beta 2 -stimulating agent should be administered concomitantly, and the lowest possible dose of metoprolol should be used. In these circumstances it would be prudent initially to administer metoprolol in smaller doses three times daily, instead of larger doses two times daily, to avoid the higher plasma levels associated with the longer dosing interval (see DOSAGE AND ADMINISTRATION ).
Major Surgery:Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
Diabetes and Hypoglycemia:Metoprolol should be used with caution in diabetic patients if a beta-blocking agent is required. Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.
Pheochromocytoma:If metoprolol is used in the setting of pheochromocytoma, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal muscle.
Thyrotoxicosis:Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade, which might precipitate a thyroid storm.
Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function, and beta-blockade carries the potential hazard of depressing myocardial contractility and precipitating or exacerbating minimal cardiac failure.
During treatment with metoprolol, the hemodynamic status of the patient should be carefully monitored. If heart failure occurs or persists despite appropriate treatment, metoprolol should be discontinued.
Bradycardia: Metoprolol produces a decrease in sinus heart rate in most patients; this decrease is greatest among patients with high initial heart rates and least among patients with low initial heart rates. Acute myocardial infarction (particularly inferior infarction) may in itself produce significant lowering of the sinus rate. If the sinus rate decreases to < 40 beats/min, particularly if associated with evidence of lowered cardiac output, atropine (0.25 to 0.5 mg) should be administered intravenously. If treatment with atropine
AV Block: If hypotension (systolic blood pressure ≤ 90 mmHg) occurs, metoprolol should be discontinued, and the hemodynamic status of the patient and the extent of myocardial damage carefully assessed. Invasive monitoring of central venous, pulmonary capillary wedge, and arterial pressures may be required. Appropriate therapy with fluids, positive inotropic agents, balloon counterpulsation, or other treatment modalities should be instituted. If hypotension is associated with sinus bradycardia or AV block, treatment should be directed at reversing these (see above).
Hypotension: If hypotension (systolic blood pressure ≤90 mmHg) occurs, metoprolol should be discontinued, and the hemodynamic status of the patient and the extent of myocardial damage carefully assessed. Invasive monitoring of central venous, pulmonary capillary wedge, and arterial pressures may be required. Appropriate therapy with fluids, positive inotropic agents, balloon counterpulsation, or other treatment modalities should be instituted. If hypotension is associated with sinus bradycardia or AV block, treatment should be directed at reversing these (see above).
Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS, including metoprolol. Because of its relative beta1 selectivity, metoprolol may be used with extreme caution in patients with bronchospastic disease. Because it is unknown to what extent beta 2 -stimulating agents may exacerbate myocardial ischemia and the extent of infarction, these agents should not be used prophylactically. If bronchospasm not related to congestive heart failure occurs, metoprolol should be discontinued. A theophylline derivative or a beta2 agonist may be administered cautiously, depending on the clinical condition of the patient. Both theophylline derivatives and beta2 agonists may produce serious cardiac arrhythmias.
Metoprolol should be used with caution in patients with impaired hepatic function.
Patients should be advised (1) to avoid operating automobiles and machinery or engaging in other tasks requiring alertness until the patient’s response to therapy with metoprolol has been determined; (2) to contact the physician if any difficulty in breathing occurs; (3) to inform the physician or dentist before any type of surgery that he or she is taking metoprolol.
Catecholamine-depleting drugs (e.g., reserpine) may have an additive effect when given with beta-blocking agents. Patients treated with metoprolol plus a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Risk of Anaphylactic Reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
Some inhalation anesthetics may enhance the cardiodepressant effect of beta-blockers (see WARNINGS, Major Surgery ).
Potent inhibitors of the CYP2D6 enzyme may increase the plasma concentration of metoprolol. Strong inhibition of CYP2D6 would mimic the pharmacokinetics of CYP2D6 poor metabolizer (see CLINICAL PHARMACOLOGY, Pharmacokinetics subsection ). Caution should therefore be exercised when coadministering potent CYP2D6 inhibitors with metoprolol. Known clinically significant potent inhibitors of CYP2D6 are antidepressants such as fluoxetine, paroxetine or bupropion, antipsychotics such as thioridazine, antiarrhythmics such as quinidine or propafenone, antiretrovirals such as ritonavir, antihistamines such as diphenhydramine, antimalarials such as hydroxychloroquine or quinidine, antifungals such as terbinafine and medications for stomach ulcers such as cimetidine.
If a patient is treated with clonidine and metoprolol concurrently, and clonidine treatment is to be discontinued, metoprolol should be stopped several days before clonidine is withdrawn. Rebound hypertension that can follow withdrawal of clonidine may be increased in patients receiving concurrent beta-blocker treatment.
Long-term studies in animals have been conducted to evaluate carcinogenic potential. In a 2-year study in rats at three oral dosage levels of up to 800 mg/kg per day, there was no increase in the development of spontaneously occurring benign or malignant neoplasms of any type. The only histologic changes that appeared to be drug related were an increased incidence of generally mild focal accumulation of foamy macrophages in pulmonary alveoli and a slight increase in biliary hyperplasia. In a 21-month study in Swiss albino mice at three oral dosage levels of up to 750 mg/kg per day, benign lung tumors (small adenomas) occurred more frequently in female mice receiving the highest dose than in untreated control animals. There was no increase in malignant or total (benign plus malignant) lung tumors, or in the overall incidence of tumors or malignant tumors. This 21-month study was repeated in CD-1 mice, and no statistically or biologically significant differences were observed between treated and control mice of either sex for any type of tumor.
All mutagenicity tests performed (a dominant lethal study in mice, chromosome studies in somatic cells, a Salmonella/mammalian-microsome mutagenicity test, and a nucleus anomaly test in somatic interphase nuclei) were negative.
No evidence of impaired fertility due to metoprolol was observed in a study performed in rats at doses up to 55.5 times the maximum daily human dose of 450 mg.
.
Metoprolol has been shown to increase postimplantation loss and decrease neonatal survival in rats at doses up to 55.5 times the maximum daily human dose of 450 mg. Distribution studies in mice confirm exposure of the fetus when metoprolol is administered to the pregnant animal. These studies have revealed no evidence of impaired fertility or teratogenicity. There are 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.
Metoprolol is excreted in breast milk in a very small quantity. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug. Caution should be exercised when metoprolol is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Clinical trials of metoprolol in hypertension did not include sufficient numbers of elderly patients to determine whether patients over 65 years of age differ from younger subjects in their response to metoprolol. Other reported clinical experience in elderly hypertensive patients has not identified any difference in response from younger patients.
In worldwide clinical trials of metoprolol tartrate in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. Other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. However, greater sensitivity of some elderly individuals taking metoprolol tartrate cannot be categorically ruled out. Therefore, in general, it is recommended that dosing proceed with caution in this population.
Most adverse effects have been mild and transient.
Central Nervous System:Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported.
Cardiovascular:Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; and hypotension have been reported in about 1 of 100 patients. Gangrene in patients with pre-existing severe peripheral circulatory disorders has also been reported very rarely. (See CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS .)
Respiratory:Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients (see WARNINGS ). Rhinitis has also been reported.
Gastrointestinal:Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients. Vomiting was a common occurrence. Post-marketing experience reveals very rare reports of hepatitis, jaundice and non-specific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic dehydrogenase elevations have also been reported.
Hypersensitive Reactions:Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis has been reported.
Miscellaneous:Peyronie’s disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, and tinnitus have also been reported.
There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. There have been very rare reports of weight gain, arthritis, and retroperitoneal fibrosis (relationship to metoprolol has not been definitely established).
The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with metoprolol.
Central Nervous System: Tiredness has been reported in about 1 of 100 patients. Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear.
Cardiovascular: In the randomized comparison of metoprolol and placebo described in theCLINICAL PHARMACOLOGY section, the following adverse reactions were reported:
| Metoprolol | Placebo | |
| Hypotension (systolic BP <90 mmHg) | 27.4% | 23.2% |
| Bradycardia (heart rate <40 beats/min) | 15.9% | 6.7% |
| Second- or third-degree heart block | 4.7% | 4.7% |
| First-degree heart block (P-R ≥0.26 sec) | 5.3% | 1.9% |
| Heart failure | 27.5% | 29.6% |
Respiratory:Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients.
Gastrointestinal:Nausea and abdominal pain have been reported in fewer than 1 of 100 patients.
Dermatologic:Rash and worsened psoriasis have been reported, but a drug relationship is not clear.
Miscellaneous:Unstable diabetes and claudication have been reported, but a drug relationship is not clear.
A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to metoprolol.
Central Nervous System:Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics.
Cardiovascular:Intensification of AV block (see CONTRAINDICATIONS ).
Hematologic:Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.
Hypersensitive Reactions:Fever combined with aching and sore throat, laryngospasm, and respiratory distress.
The following adverse reactions have been reported during post-approval use of metoprolol: confusional state, an increase in blood triglycerides and a decrease in High Density Lipoprotein (HDL). Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency.
To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Several cases of overdosage have been reported, some leading to death.
Oral LD50’s (mg/kg): mice, 1158 - 2460; rats, 3090 - 4670.
Potential signs and symptoms associated with overdosage with metoprolol are bradycardia, hypotension, bronchospasm, and cardiac failure.
There is no specific antidote.
In general, patients with acute or recent myocardial infarction may be more hemodynamically unstable than other patients and should be treated accordingly (see WARNINGS, Myocardial Infarction ).
On the basis of the pharmacologic actions of metoprolol, the following general measures should be employed:
Bradycardia:Atropine should be administered. If there is no response to vagal blockade, isoproterenol should be administered cautiously.
Hypotension:A vasopressor should be administered, e.g., levarterenol or dopamine.
Bronchospasm:A beta 2 -stimulating agent and/or a theophylline derivative should be administered.
Cardiac Failure:A digitalis glycoside and diuretic should be administered. In shock resulting from inadequate cardiac contractility, administration of dobutamine, isoproterenol, or glucagon may be considered.
Early Treatment: During the early phase of definite or suspected acute myocardial infarction, treatment with metoprolol can be initiated as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized.
Treatment in this early phase should begin with the intravenous administration of three bolus injections of 5 mg of metoprolol each; the injections should be given at approximately 2-minute intervals. During the intravenous administration of metoprolol, blood pressure, heart rate, and electrocardiogram should be carefully monitored.
In patients who tolerate the full intravenous dose (15 mg), metoprolol tablets, 50 mg every 6 hours, should be initiated 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, patients should receive a maintenance dosage of 100 mg twice daily (see DOSAGE AND ADMINISTRATION, Late Treatment below ).
Patients who appear not to tolerate the full intravenous dose should be started on metoprolol tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last
Late Treatment: Patients with contraindications to treatment during the early phase of suspected or definite myocardial infarction, patients who appear not to tolerate the full early treatment, and patients in whom the physician wishes to delay therapy for any other reason should be started on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Therapy should be continued for at least 3 months. Although the efficacy of metoprolol beyond 3 months has not been conclusively established, data from studies with other beta-blockers suggest that treatment should be continued for 1 - 3 years.
Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Metoprolol Tartrate Injection, USP is a clear and colorless solution available as:
5 mL Single Dose Vials – each containing 5 mg Metoprolol Tartrate, USP.
Cartons of 10 vials NDC 0143-9873-10
Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].
Protect from light. Do not freeze.
Retain in carton until time of use.
Manufactured by:
HIKMA FARMACÊUTICA (PORTUGAL), S.A.
Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT,
PORTUGAL
Distributed by:
WEST-WARD PHARMACEUTICAL CORP.
Eatontown, NJ 07724 USA
Revised: 12/2011
Metoprolol Tartrate Injection, USP
5 mg/5 mL
(1 mg/mL)
NDC 0143-9873-10
| METOPROLOL TARTRATE metoprolol tartrate injection, solution | ||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| ANDA | ANDA077761 | 05/30/2007 | |
| Labeler - West-ward Pharmaceutical Corp (001230762) |
