Визидол глазные капли инструкция по применению

Инструкция по медицинскому применению лекарственного средства ВизидолФорма выпуска и состав

Состав: активное вещество — кеторолак трометамин — 5 мг вспомогательные вещества: натрия хлорид — 7,9 мг; динатрия эдетат — 1 мг октоксинол 40 — 0,1 мг; бензалкония хлорид — 0/1 мг; натрия гидроксид и/или кислота хлористоводородная до рН 7,4, вода для инъекций — до 1 мл. Форма выпуска Во флаконах-капельницах из полиэтилена по 5 мл.

Фармакологическое действие

При местном применении в глаз оказывает выраженное анальгезирующее и умеренное противовоспалительное действие, обусловленное угнетением активности циклооксигеназы — основного фермента метаболизма арахидоновой кислоты. Это приводит к снижению уровня простагландинов во влаге передней камеры глаза, играющих главную роль в патогенезе воспаления и боли. Препарат не влияет на внутриглазное давление. При инстилляции в глаз системная абсорбция препарата очень низкая.

Показания

— Снижение боли и предупреждение воспаления в послеоперационном периоде после удаления катаракты и других хирургических вмешательств на переднем сегменте глаза. — Воспалительно-болевой синдром при заболеваниях переднего отдела глаза неинфекционной природы (в том числе хронический неинфекционный конъюнктивит). — Снятие покалывания в глазах при сезоном аллергическом конъюнктивите.

Режим дозирования

Препарат применяют взрослым и детям старше 12 лет инстилляционно в конъюнктивальный мешок. Перед операцией: по 1 капле 5 раз в течение 3 часов до операции. В послеоперационном периоде: по 1 капле 3 раза в день сразу после операции; далее по 1 капле 4 раза в день в течение необходимого для лечения времени (7-10 дней). При лечении воспалительно-болевого синдрома, для снятия покалывания в глазах при сезонном аллергическом конъюнктивите: по 1 капле 4 раза в день до клинического излечения, но не более 10 дней.

Побочное действие

Проходящее жжение и покалывание после инстилляции, аллергические реакции, отек роговицы, кератит поверхностный. При применении более 14 дней возможно повреждение целостности роговицы: утончение, эрозия, изъязвление и перфорация; синдром «сухого глаза», присоединение глазной инфекции. При длительном бесконтрольном применении у отдельных пациентов могут наблюдаться системные побочные эффекты — головная боль, головокружение, сонливость, повышение артериального давления. В случае возникновения любых побочных реакций необходимо обязательно посоветоваться с врачом относительно дальнейшего применения препарата!

Противопоказания к применению

— Повышенная чувствительность к кеторолаку и другим нестероидным противовоспалительным средствам. — Кровоизлияния в мозг. — Беременность и период кормления грудью. — Препарат не рекомендуется назначать детям в возрасте до 12 лет. — Не установлена эффективность и безопасность применения препарата у детей до трех лет.

При беременности и кормлении

Препарат противопоказан к применению при беременности и в период кормления грудью.

Особые указания

С осторожностью применяют у пациентов с пониженной свертываемостью крови в анамнезе. При ношении мягких контактных линз необходимо снять линзы за пять минут до инстилляции и надеть через 15 мин после принятия лекарства. Влияние на способность водить и использовать машины С осторожностью применять пациентам, у которых после аппликации временно теряется четкость зрения; не рекомендуется водить машину или работать со сложной техникой, станками или каким-либо сложным оборудованием, требующим четкости зрения сразу после закапывания.

Передозировка

При соблюдении способа применения передозировка невозможна. В случае ухудшения состояния или возникновения аллергических реакций следует прекратить прием препарата и обратиться к врачу.

Лекарственное взаимодействие

Если вы принимаете какие-либо другие лекарственные средства, обязательно проконсультируйтесь с врачом о возможности применения препарата! В случае необходимости, препарат можно комбинировать с глазными каплями, содержащими антибиотики, бета-блокаторы, ингибиторы карбоангидразы и мидриатики; перерыв между закапываниями должен быть не менее 5 минут. При комбинации со стероидами удлиняется процесс заживления раны. При одновременном применении с другими нестероидными противовоспалительными средствами, пентоксифиллином, антикоагулянтами возможно увеличение риска послеоперационного кровотечения.

Условия и сроки хранения

Условия хранения При температуре от 15 до 30°С в недоступном для детей месте. Срок годности 2 года. Не использовать после истечения срока годности, указанного на упаковке. После вскрытия содержимое флакона использовать в течение месяца.

Описание ВизиДол 0.5%

Торговое название: 

ВизиДол™

Международное непатентованное название 

 кеторолак.

Лекарственная форма: 

капли глазные 0,5 %.
Активное вещество – кеторолак трометамин – 5 мг/мл.

Описание: 

Бесцветная или слегка желтоватая прозрачная жидкость.

Фармакотерапевтическая группа 

 нестероидное противовоспалительное средство

Код АТХ: S01BC05

Фармакологическое действие

При местном применении в глаз оказывает выраженное анальгезирующее и умеренное противовоспалительное действие, обусловленное угнетением активности циклооксигеназы — основного фермента метаболизма арахидоновой кислоты. Это приводит к снижению уровня простагландинов во влаге передней камеры глаза, играющих главную роль в патогенезе воспаления и боли. Препарат не влияет на внутриглазное давление. При инстилляции в глаз системная абсорбция препарата очень низкая.

Показания

Снижение боли и предупреждение воспаления в послеоперационном периоде после удаления катаракты и других хирургических вмешательств на переднем сегменте глаза. Воспалительно-болевой синдром при заболеваниях переднего отдела глаза неинфекционной природы (в том числе хронический неинфекционный конъюнктивит). Снятие покалывания  в глазах при сезонном аллергическом конъюнктивите.

Способ применения и дозы

Препарат применяют взрослым и детям старше 12 лет инстилляционно в конъюнктивальный мешок. Перед операцией: по 1 капле 5 раз в течение 3 часов до операции. В послеоперационном периоде: по 1 капле 3 раза в день сразу после операции; далее по 1 капле 4 раза в день в течение необходимого для лечения времени (7-10 дней). При лечении воспалительно-болевого синдрома, для снятия покалывания  в глазах при сезонном аллергическом конъюнктивите:  по 1 капле 4 раза в день до клинического излечения, но не более 10 дней.

Побочные эффекты

Проходящее жжение и покалывание после инстилляции, аллергические реакции, отек роговицы, кератит поверхностный.
При применении более 14 дней возможно повреждение целостности роговицы: утончение, эрозия, изъязвление и перфорация; синдром «сухого глаза», присоединение глазной инфекции.
При длительном бесконтрольном применении у отдельных пациентов могут наблюдаться системные побочные эффекты — головная боль, головокружение, сонливость, повышение артериального давления.
В случае возникновения любых побочных реакций необходимо обязательно посоветоваться с врачом относительно дальнейшего применения препарата!

Противопоказания

Повышенная чувствительность к кеторолаку и другим нестероидным противовоспалительным средствам. Кровоизлияния в мозг. Беременность и период кормления грудью. Препарат не рекомендуется назначать детям в возрасте до 12 лет. Не установлена эффективность и безопасность применения препарата у детей до трех лет.

Передозировка

При соблюдении способа применения передозировка невозможна. В случае ухудшения состояния или возникновения аллергических реакций следует прекратить прием препарата и обратиться к врачу.

Предостережения

Если симптомы заболевания не исчезают, или же наоборот, состояние здоровья ухудшается, или появляются нежелательные явления, необходимо прекратить прием препарата и обратиться за консультацией к врачу относительно дальнейшего применения препарата.

Взаимодействие с лекарственными средствами

Если вы принимаете какие-либо другие лекарственные средства, обязательно проконсультируйтесь с врачом о возможности применения препарата!
В случае необходимости, препарат можно комбинировать с глазными каплями, содержащими антибиотики, бета-блокаторы, ингибиторы карбоангидразы и мидриатики; перерыв между закапываниями должен быть не менее 5 минут. При комбинации со стероидами удлиняется процесс заживления раны.
При одновременном применении с другими нестероидными противовоспалительными средствами, пентоксифиллином, антикоагулянтами возможно увеличение риска послеоперационного кровотечения.

Особые указания

С осторожностью применяют у пациентов с пониженной свертываемостью крови в анамнезе.
При ношении мягких контактных линз необходимо снять линзы за пять минут до инстилляции и надеть через 15 мин после принятия лекарства.

Влияние на способность водить и использовать машины

С осторожностью применять пациентам, у которых после аппликации временно теряется четкость зрения; не рекомендуется водить машину или работать со сложной техникой, станками или каким-либо сложным оборудованием, требующим четкости зрения сразу после закапывания.

Применение в период беременности и  лактации

Препарат противопоказан к применению при беременности и в период лактации.
Условия  хранения
При температуре от 15 до 30 оС в недоступном для детей месте.

Срок годности

2 года. Не использовать после истечения срока годности, указанного на упаковке. После вскрытия содержимое флакона использовать в течение месяца.

Форма выпуска

Во флаконах-капельницах из полиэтилена по 5 мл.

Условия отпуска

Отпускается по рецепту.

It is recommended that Vizidol be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

In common with other anti-inflammatory drugs, Vizidol may mask the usual signs of infection.

All non-steroidal anti-inflammatory drugs (NSAIDs) may slow down or delay wound healing. Concomitant use of NSAIDs and topical steroids can increase the potential for healing problems.

Concomitant use of Vizidol and topical corticosteroids should be exercised with caution in patients susceptible to corneal epithelial breakdown.

Use of topical NSAIDS may result in keratitis. In some patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Topical NSAIDs should be used with caution in patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g. dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time, as they may be at increased risk for corneal adverse events which may become sight threatening.

Post marketing experience with topical NSAIDs also suggest that use more than 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events.

The preservative in Vizidol, benzalkonium chloride, may cause eye irritation. Contact lenses must be removed prior to application, with at least a 15-minute wait before reinsertion. Benzalkonium chloride is known to discolour soft contact lenses. Contact with soft contact lenses must be avoided.

There have been post-marketing reports of bronchospasm or exacerbation of asthma in patients, who have either a known hypersensitivity to aspirin/non-steroidal anti-inflammatory drugs or a past medical history of asthma associated with the use of Vizidol, which may be contributory. Caution is recommended in the use of Vizidol in these individuals.

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures to avoid injury and contamination of eye drops.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.

WARNINGS

(see also BOXED WARNING)

The total combined duration of use of Vizidol^ORAL and IV or IM dosing of ketorolac tromethamine is not to exceed 5 days in adults. Vizidol (ketorolac tromethamine) ^ORAL is not indicated for use in pediatric patients.

The most serious risks associated with Vizidol (ketorolac tromethamine) are:

Gastrointestinal Effects — Risk of Ulceration, Bleeding, and Perforation

Vizidol (ketorolac tromethamine) is contraindicated in patients with previously documented peptic ulcers and/or GI bleeding. Vizidol (ketorolac tromethamine) can cause serious gastrointestinal (GI) adverse events including bleeding, ulceration and perforation, of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with Vizidol (ketorolac tromethamine).

Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Minor upper gastrointestinal problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. The incidence and severity of gastrointestinal complications increases with increasing dose of, and duration of treatment with, Vizidol (ketorolac tromethamine). Do not use Vizidol (ketorolac tromethamine) for more than five days. However, even short-term therapy is not without risk. In addition to past history of ulcer disease, other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids, or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of Vizidol (ketorolac tromethamine) until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated.

Hemorrhage

Because prostaglandins play an important role in hemostasis and NSAIDs affect platelet aggregation as well, use of Vizidol (ketorolac tromethamine) in patients who have coagulation disorders should be undertaken very cautiously, and those patients should be carefully monitored. Patients on therapeutic doses of anticoagulants (eg, heparin or dicumarol derivatives) have an increased risk of bleeding complications if given Vizidol (ketorolac tromethamine) concurrently; therefore, physicians should administer such concomitant therapy only extremely cautiously. The concurrent use of Vizidol (ketorolac tromethamine) and therapy that affects hemostasis, including prophylactic low-dose heparin (2500 to 5000 units q12h), warfarin and dextrans have not been studied extensively, but may also be associated with an increased risk of bleeding. Until data from such studies are available, physicians should carefully weigh the benefits against the risks and use such concomitant therapy in these patients only extremely cautiously. Patients receiving therapy that affects hemostasis should be monitored closely.

In postmarketing experience, postoperative hematomas and other signs of wound bleeding have been reported in association with the peri-operative use of IV or IM dosing of ketorolac tromethamine. Therefore, peri-operative use of Vizidol (ketorolac tromethamine) should be avoided and postoperative use be undertaken with caution when hemostasis is critical (see PRECAUTIONS).

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

Vizidol (ketorolac tromethamine) and its metabolites are eliminated primarily by the kidneys, which, in patients with reduced creatinine clearance, will result in diminished clearance of the drug (see CLINICAL PHARMACOLOGY). Therefore, Vizidol (ketorolac tromethamine) should be used with caution in patients with impaired renal function (see DOSAGE AND ADMINISTRATION) and such patients should be followed closely. With the use of Vizidol (ketorolac tromethamine) , there have been reports of acute renal failure, interstitial nephritis and nephrotic syndrome.

Impaired Renal Function

Vizidol (ketorolac tromethamine) is contraindicated in patients with serum creatinine concentrations indicating advanced renal impairment (see CONTRAINDICATIONS). Vizidol (ketorolac tromethamine) should be used with caution in patients with impaired renal function or a history of kidney disease because it is a potent inhibitor of prostaglandin synthesis. Because patients with underlying renal insufficiency are at increased risk of developing acute renal decompensation or failure, the risks and benefits should be assessed prior to giving Vizidol (ketorolac tromethamine) to these patients.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without a known previous exposure or hypersensitivity to Vizidol (ketorolac tromethamine). Vizidol (ketorolac tromethamine) should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS: Preexisting Asthma). Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome. Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Cardiovascular Effects

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see Gastrointestinal Effects — Risk of Ulceration, Bleeding, and Perforation). Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).

Hypertension

NSAIDs, including Vizidol (ketorolac tromethamine) , can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Vizidol (ketorolac tromethamine) , should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Congestive Heart Failure and Edema

Fluid retention, edema, retention of NaCl, oliguria, elevations of serum urea nitrogen and creatinine have been reported in clinical trials with Vizidol (ketorolac tromethamine). Therefore, Vizidol (ketorolac tromethamine) should be used only very cautiously in patients with cardiac decompensation, hypertension or similar conditions.

Skin Reactions

NSAIDS, including Vizidol (ketorolac tromethamine) , can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Pregnancy

In late pregnancy, as with other NSAIDs, Vizidol (ketorolac tromethamine) should be avoided because it may cause premature closure of the ductus arteriosus.

PRECAUTIONS

General

Vizidol (ketorolac tromethamine) cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of Vizidol (ketorolac tromethamine) in reducing inflammation may diminish the utility of this diagnostic sign in detecting complications of presumed noninfectious, painful conditions.

Hepatic Effect

Vizidol (ketorolac tromethamine) should be used with caution in patients with impaired hepatic function or a history of liver disease. Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Vizidol (ketorolac tromethamine). These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Vizidol (ketorolac tromethamine). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), Vizidol (ketorolac tromethamine) should be discontinued.

Hematologic Effect

Anemia is sometimes seen in patients receiving NSAIDs, including Vizidol (ketorolac tromethamine). This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Vizidol (ketorolac tromethamine) , should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Vizidol (ketorolac tromethamine) who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Preexisting Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Vizidol (ketorolac tromethamine) should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Information for Patients

Vizidol (ketorolac tromethamine) is a potent NSAID and may cause serious side effects such as gastrointestinal bleeding or kidney failure, which may result in hospitalization and even fatal outcome.

Physicians, when prescribing Vizidol (ketorolac tromethamine) , should inform their patients or their guardians of the potential risks of Vizidol treatment (see BOXED WARNING, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS sections), instruct patients to seek medical advice if they develop treatment-related adverse events, and advise patients not to give Vizidol (ketorolac tromethamine) ^ORAL to other family members and to discard any unused drug.

Remember that the total combined duration of use of Vizidol^ORAL and IV or IM dosing of ketorolac tromethamine is not to exceed 5 days in adults. Vizidol (ketorolac tromethamine) ^ORAL is not indicated for use in pediatric patients.

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

1. Vizidol (ketorolac tromethamine) , like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS: Cardiovascular Effects).
2. Vizidol (ketorolac tromethamine) , like other NSAIDs, can cause GI discomfort and rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS: Gastrointestinal Effects — Risk of Ulceration, Bleeding, and Perforation).
3. Vizidol (ketorolac tromethamine) , like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
4. Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
5. Patients should be informed of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
6. Patients should be informed of the signs of an anaphylactoid reaction (eg, difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
7. In late pregnancy, as with other NSAIDs, Vizidol (ketorolac tromethamine) should be avoided because it will cause premature closure of the ductus arteriosus.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs, should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (eg, eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Vizidol (ketorolac tromethamine) should be discontinued.

Carcinogenesis, Mutagenesis and Impairment of Fertility

An 18-month study in mice with oral doses of ketorolac tromethamine at 2 mg/kg/day (0.9 times the human systemic exposure at the recommended IM or IV dose of 30 mg qid, based on area-under-the-plasma-concentration curve [AUC]), and a 24-month study in rats at 5 mg/kg/day (0.5 times the human AUC) showed no evidence of tumorigenicity. Ketorolac tromethamine was not mutagenic in the Ames test, unscheduled DNA synthesis and repair, and in forward mutation assays.

Ketorolac tromethamine did not cause chromosome breakage in the in vivo mouse micronucleus assay. At 1590 μg/mL and at higher concentrations, ketorolac tromethamine increased the incidence of chromosomal aberrations in Chinese hamster ovarian cells.

Impairment of fertility did not occur in male or female rats at oral doses of 9 mg/kg (0.9 times the human AUC) and 16 mg/kg (1.6 times the human AUC) of ketorolac tromethamine, respectively.

Pregnancy

Teratogenic Effects: Pregnancy Category C

Reproduction studies have been performed during organogenesis using daily oral doses of ketorolac tromethamine at 3.6 mg/kg (0.37 times the human AUC) in rabbits and at 10 mg/kg (1.0 times the human AUC) in rats. Results of these studies did not reveal evidence of teratogenicity to the fetus. However, animal reproduction studies are not always predictive of human response.

Nonteratogenic Effects

Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided. Oral doses of ketorolac tromethamine at 1.5 mg/kg (0.14 times the human AUC), administered after gestation Day 17, caused dystocia and higher pup mortality in rats.

There are no adequate and well-controlled studies of Vizidol (ketorolac tromethamine) in pregnant women. Vizidol (ketorolac tromethamine) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The use of Vizidol (ketorolac tromethamine) is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage (see CONTRAINDICATIONS).

Effects on Fertility

The use of ketorolac tromethamine, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of infertility, withdrawal of ketorolac tromethamine should be considered.

Nursing Mothers

After a single administration of 10 mg of Vizidol (ketorolac tromethamine) ^ORAL to humans, the maximum milk concentration observed was 7.3 ng/mL, and the maximum milk-to-plasma ratio was 0.037. After 1 day of dosing (qid), the maximum milk concentration was 7.9 ng/mL, and the maximum milk-to-plasma ratio was 0.025. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use in nursing mothers is contraindicated.

Pediatric Use

Vizidol (ketorolac tromethamine) ^ORAL is not indicated for use in pediatric patients. The safety and effectiveness of Vizidol (ketorolac tromethamine) ^ORAL in pediatric patients below the age of 17 have not been established.

Geriatric Use ( ≥ 65 years of age)

Because ketorolac tromethamine may be cleared more slowly by the elderly (see CLINICAL PHARMACOLOGY) who are also more sensitive to the dose-related adverse effects of NSAIDs (see WARNINGS: Gastrointestinal Effects — Risk of Ulceration, Bleeding, and Perforation), extreme caution, reduced dosages (see DOSAGE AND ADMINISTRATION), and careful clinical monitoring must be used when treating the elderly with Vizidol (ketorolac tromethamine).