Brexidol 20mg tablets

Brexidol 20 mg Tablets

piroxicam betadex

Important things you need to know about Brexidol.

• 
  Brexidol is a non-steroidal anti-inflammatory medicine, prescribed to relieve the symptoms of arthritis.


• 
  You need to take it regularly to get the maximum benefit. Do not stop taking it without talking to your doctor.


• 
  Brexidol can cause side effects in some people (read Section 4 for details).
  If you have any signs of bleeding in the stomach or intestines or vomit blood, stop taking your tablets and contact your doctor immediatly.


• 
  Your doctor will regularly monitor your condition to check you are taking the correct dose of Brexidol.


• 
  Your doctor may prescribe other medicines for you to take at the same time as Brexidol to protect your stomach and intestines.


• 
  Taking other medicines, including other NSAIDs, may sometimes cause problems. Check with your doctor or pharmacist before taking any other medicines.

Now read the rest of this leaflet. It includes other important information on the safe use of this medicine that might be especially important for you.This leaflet was last updated on 12/2008.

In this leaflet:

• 
  1. What Brexidol is and what it is used for
  


• 
  2. Before you take Brexidol
  


• 
  3. How to take Brexidol
  


• 
  4. Possible side effects
  


• 
  5. How to store Brexidol
  


• 
  6. Further information
  

What Brexidol is and what it is used for

Brexidol Tablets contain piroxicam which belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs) that reduce pain and inflammation. The piroxicam is present as a fast acting form called piroxicam betadex, allowing quicker absorption by the body to give rapid pain relief.

Before prescribing Brexidol, your doctor will assess the benefits this medicine may give you against your risk of developing side effects and may need to give you check-ups from time to time.

Your doctor will prescribe Brexidol only when you have had unsatisfactory relief of symptoms from other non-steroidal anti-inflammatory medicines (NSAIDs).

Brexidol Tablets relieve swelling, stiffness and joint pain in the following conditions:

• osteoarthritis (arthrosis, degenerative joint disease)


• rheumatoid arthritis


• ankylosing spondylitis (form of spinal arthritis)

These tablets do not cure arthritis but will help you only as long as you continue to take them.

Before you take Brexidol

Do not take Brexidol:

• if you previously had a senous allergic drug reaction to piroxicam, other NSAIDs, other medications or any of the other ingredients in the tablets (these are listed in Section 6,Further Information), especially serious skin reactions (regardless of severity) such as exfoliative dermatitis (intense reddening of skin, with skin peeling off in scales or layers), vesiculo-bullous reactions (Stevens-Johnson syndrome, a condition with red blistered, eroded, bloody or crusted skin) and toxic epidermal necrolysis, (a disease with blistering and peeling of the top layer of skin)


• if you have, or have ever had a stomach or intestinal ulcer, bleeding or perforation


• if you have, or have had a history of gastrointestinal disorders (inflammation of the stomach or intestines) that predispose to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancers, diverticulitis (inflammed or infected pouches/pockets in the colon)


• if you suffer from porphyria, an inherited blood disorder that can cause increased sensitivity to light


• if you have heart failure


• if you are taking anticoagulants, such as warfarin, to prevent blood clots


• if you are taking any other NSAIDs, including COX-2 selective NSAIDs and aspirin, present in many medicines used to relieve pain and lower fever


• if you are over 80 years of age

If any of these apply to you, you should not be given piroxicarn.Tell your doctor immediately.

Brexidol must not be given to children.

Take special care with Brexidol and always tell your doctor if:

• you have kidney or liver problems


• you have a history of any blood or bleeding disorder


• you have, or have ever suffered from asthma


• you have heart problems, previously had a stroke or think that you might be at risk of these conditions, (for example, if you have high blood pressure, diabetes or high cholesterol or are a smoker)


• if you have any medical condition or allergies you are unsure about


• you are over 70 years of age. Your doctor may reduce the duration of your treatment.


• you are over 70 years of age and taking other medicines such as selective serotonin re-uptake inhibitors-SSRIs (to treat depression), steroids or aspirin (to prevent blood clotting). Your doctor may prescribe other medicines for you to take at the same time as Brexidol to protect your stomach and intestines.

If any of these apply to you, your doctor may want to perform regular tests to monitor your condition and may need to carry out blood tests from time to time.

You should immediatly stop taking Brexidol and tell your doctor if you have any allergic reaction such as a skin rash, swelling of the face, wheezing or difficultly breathing.

Like all NSAIDs, Brexidol can cause serious reactions in the stomach and intestines, such as pain, bleeding, ulceration and perforation. Immediatly stop taking Brexidol and tell your doctor if you have stomach pain, or any sign of bleeding in the stomach or intestines, such as passing black or bloodstained bowel movements, or vomiting blood.

Medicines such as Brexidol may be associated with a small increased risk of heart attack or stroke. Any risk is more likely with high doses and prolonged treatment. Do not exceed the recommended dose or duration of treatment.

Taking other medicines

Before starting treatment, please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

If you have to go to a doctor, dentist or hospital for any reason, tell them that you are taking Brexidol.

In particular, tell your doctor if you are taking:

• lithium, to treat depression


• methotrexate, to treat some inflammatory diseases and cancers


• aspirin, ibuprofen or any other NSAIDs for pain relief


• ciclosporin, to treat some inflammatory diseases and after transplants


• quinolone antibiotics, such as ciprofloxacin to treat bacterial infections


• water tablets (diuretics), such as amiloride


• anticoagulants, such as warfarin to stop the blood clotting


• medicines to treat diabetes, such as gliclazide


• aminoglycosides, such as gentamycin to treat bacterial infections


• probenecid, to treat gout


• medicines to treat high blood pressure, such as beta-blockers


• cardiac glycosides, such as digoxin to treat heart problems


• mifepristone, used to terminate pregnancy


• oral steroids e.g. prednisolone, used to treat many conditions such as allergies and hormone imbalances


• cimetidine, to treat stomach ulcers


• sulphonamides, to treat bacterial infections


• hydantoins, such as phenytoin to treat seizures


• selective serotonin re-uptake inhibitors (SSRI), to treat depression


• acetylsalicyclic acid, such as aspirin to prevent platelet clumping


• zidovudine, used to treat viral infections


• tacrolimus, used to dampen down the body's immune response and maybe used for severe skin complaints and following organ transplantation.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, or could become pregnant, talk to your doctor before taking your tablets.

Brexidol may make it more difficult to become pregnant. You should inform your doctor if you are planning to become pregnant or if you have problems becoming pregnant.

Driving and using machines:

If you experience headaches, blurred vision, dizziness or drowsiness after taking these tablets, then do not drive or operate machinery.

Important information about some of the ingredients of Brexidol

Brexidol contains laclose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

How to take Brexidol

Always take your tablets exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. Your doctor will regularly monitor your condition to check you are taking the correct dose of Brexidol and adjust your treatment to the lowest dose that best controls your symptoms. Under no circumstances should you change the dose without first speaking to your doctor. If you feel this medicine is not effective, talk to your doctor.

You should take the lowest dose for the shortest time necessary to minimise side effects.

Dosage

• Brexidol is formulated so that you only have to take your tablets once a day. The label on the carton will tell you how many tablets you should take and when.


• Your doctor may tell you to take half a tablet. To halve a tablet, place it on a flat surface so that you can see the score line and press gently with your thumb.


• Take your tablets at the same time each day, with or after food.


• Your doctor may prescribe other medicines for you to take at the same time as Brexidol to protect your stomach and intestines.


• 
  Do not stop treatment or change your dose even if you feel better unless told to do so by your doctor.

Adults and the elderly

The maximum daily dose is one Brexidol 20 mg tablet once a day

If you are older than 70 years of age your doctor may prescribe a lower daily dose for you to take and reduce your duration of treatment.

Children must not take this medicine.

If you take more Brexidol than you should

If you accidentally take more Brexidol than you should, contact your nearest casualty department or tell your doctor or pharmacist immediately. Remember to take the pack and any remaining tablets with you.

If you forget to take Brexidol

Do not worry. Simply leave out that dose completely and then take your next dose at the right time. Do not take a double dose to make up for a missed dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Brexidol can cause side effects, although not everyone gets them.

Allergic reactions have been reported. If you experience any of these, contact your doctor or nearest casualty department immediately.

• tight chest, severe difficulty in breathing or anaphylaxis where symptoms may be a rapid pulse, profuse sweating, fever and if severe, shock and collapse


• skin rashes including itching, "nettle" rash or hives, a serious reaction causing swelling of the face or throat, a serious illness with blistering of the skin, mouth, eyes and genitals (Stevens-Johnson Syndrome), unusual bruising, intense reddening with skin peeling off in scales or layers, blistering and peeling of the top layer of skin


• loosening and splitting of nails and hair loss


• swelling of blood vessels which may be associated with fever, rash and joint pains.

If you experience any of the following serious side effects stop taking your tablets and contact your doctor or nearest casualty department immediately.

• blood in the stools or bloody diarrhoea


• perforation or ulcers of the stomach or small intestine


• vomiting blood


• abdominal or stomach pain

The following side effects have also been reported, tell your doctor or pharmacist if you notice any of these:

• sensitivity to sunlight


• changes in the way your kidneys work, including kidney failure


• reduction in red blood cells which can make the skin pale and cause weakness or breathlessness


• reduction in blood platelets, which increases risk of bleeding or bruising


• severe reduction in blood cells which can cause weakness, bruising or make infections more likely


• reduction in number of white blood cells which make infection more likely


• nosebleed


• swelling of your feet and ankles


• changes in liver function that may cause yellowing of the skin or eyes or affect the results from liver function tests


• high blood pressure


• heart failure


• headache


• tiredness and drowsiness


• difficulty in sleeping


• depression


• nervousness


• hallucinations


• mood changes


• nightmares


• confusion


• pins and needles


• dizziness or 'spinning'


• blurred vision


• painful inflammation of the optic nerve in your eye


• ringing in the ears


• feeling generally unwell


• feeling your heartbeat


• low sugar levels in the blood resulting in tremors, sweating and raised pulse rate


• weight loss or gain


• impaired hearing


• mouth ulcers


• loss of appetite


• feeling sick


• constipation


• flatulence


• diarrhoea


• indigestion


• vomiting

Medicines such as Brexidol maybe associated with a small increased risk of heart attack (myocardial infarction) or stroke.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Brexidol

• Keep out of the reach and sight of children.


• Do not use Brexidol after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of that month.


• This medicinal product does not require any special storage conditions.


• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

Further Information

What Brexidol contains:

The active substance in your tablets is piroxicam. Each tablet contains 20 mg of piroxicam betadex.

The other ingredients are lactose monohydrate, crospovidone, sodium starch glycollate, colloidal silicon dioxide, pregelatinised starch and magnesium stearate.

What Brexidol looks like and the contents of the pack:

Brexidol 20 mg tablets are pale yellow, hexagonal tablets, marked with a score line in the middle on one side. They are packed in blister packs of 30 tablets.

Marketing Authorisation Holder:

Chiesi Limited

Cheadle Royal Business Park

Highfield

Cheadle

SK8 3GY

UK

Manufacturer:

Chiesi Farmaceutici S.p.A.

Via Palermo 26/A

43100 Parma

Italy

Is this leaflet hard to see or read? Phone 0161 488 5555 for help.

CP0003/8

87J55.04/01

Hydralazine and Hydrochlorothiazide

Dosage Form: capsules

WARNING:THIS FIXED-COMBINATION DRUG IS NOT INDICATED FOR INITIAL THERAPY OF HYPERTENSION. HYPERTENSION REQUIRES THERAPY TITRATED TO THE INDIVIDUAL PATIENT. IF THE FIXED COMBINATION REPRESENTS THE DOSAGE SO DETERMINED, ITS USE MAY BE MORE CONVENIENT IN PATIENT MANAGEMENT. THE TREATMENT OF HYPERTENSION IS NOT STATIC BUT MUST BE REEVALUATED AS CONDITIONS IN EACH PATIENT WARRANT.

Hydralazine and Hydrochlorothiazide Description

Hydralazine HCl and hydrochlorothiazide is an antihypertensive-diuretic combination available as capsules for oral administration. Hydralazine HCl and hydrochlorothiazide capsules of 25 mg/25 mg contain 25 mg of Hydralazine hydrochloride USP and 25 mg of hydrochlorothiazide USP; capsules of 50 mg/50 mg contain 50 mg of hydralazine hydrochloride USP and 50 mg of hydrochlorothiazide USP; and capsules of 100 mg/50 mg contain 100 mg of hydralazine hydrochloride USP and 50 mg of hydrochlorothiazide USP.

Each capsule also contains the following inactive ingredients: Corn starch, crospovidone, gelatin, lactose monohydrate, pharmaceutical glaze, sodium starch glycolate, stearic acid, talc, and titanium dioxide. In addition, the 25 mg/25 mg capsule contains ammonium hydroxide, ethylene glycol monoethyl ether, propylene glycol and synthetic black iron oxide; the 50 mg/50 mg capsule contains FD&C Blue #1, FD&C Red #40, FD&C Yellow #6, synthetic red iron oxide and pharmaceutical shellac; and the 100 mg/50 mg capsule contains D&C Red #28, D&C Yellow #10, FD&C Blue #1,FD&C Blue #2, FD&C Red #40, propylene glycol and synthetic black iron oxide.

Hydralazine hydrochloride is 1-hydrazinophthalazine monohydrochloride, and its structural formula is:

Hydralazine hydrochloride USP is a white to off-white, odorless crystalline powder. It is soluble in water, slightly soluble in alcohol, and very slightly soluble in ether. It melts at about 275°C, with decomposition, and has a molecular weight of 196.64.

Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, and its structural formula is:

Hydrochlorothiazide USP is a white, or practically white, practically odorless crystalline powder. It is freely soluble in sodium hydroxide solution, inn-butylamine, and in dimethylformamide; sparingly soluble in methanol; slightly soluble in water; and insoluble in ether, in chloroform, and in dilute mineral acids. Its molecular weight is 297.75.

Hydralazine and Hydrochlorothiazide - Clinical Pharmacology

Hydralazine

Although the precise mechanism of action of hydralazine is not fully understood, the major effects are on the cardiovascular system. Hydralazine apparently lowers blood pressure by exerting a peripheral vasodilating effect through a direct relaxation of vascular smooth muscle. Hydralazine, by altering cellular calcium metabolism, interferes with the calcium movements within the vascular smooth muscle that are responsible for initiating or maintaining the contractile state.

The peripheral vasodilating effect of hydralazine results in decreased arterial blood pressure (diastolic more than systolic); decreased peripheral vascular resistance; and an increased heart rate, stroke volume, and cardiac output. The preferential dilatation of arterioles, as compared to veins, minimizes postural hypotension and promotes the increase in cardiac output. Hydralazine usually increases renin activity in plasma, presumably as a result of increased secretion of renin by the renal juxtaglomerular cells in response to reflex sympathetic discharge. This increase in renin activity leads to the production of angiotensin II, which then causes stimulation of aldosterone and consequent sodium reabsorption. Hydralazine also maintains or increases renal and cerebral blood flow.

Hydrochlorothiazide

Thiazides affect the renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage, all thiazides are approximately equal in their diuretic potency. Thiazides increase excretion of sodium and chloride in approximately equivalent amounts. Natriuresis causes a secondary loss of potassium.

The mechanism of the antihypertensive effect of thiazides is unknown. Thiazides do not affect normal blood pressure.

Pharmacokinetics

Hydralazine:Hydralazine is rapidly absorbed after oral administration, and peak plasma levels are reached at 1-2 hours. Plasma levels decline with a half-life of 3-7 hours. Binding to human plasma protein is 87%. Plasma levels of hydralazine vary widely among individuals. Hydralazine is subject to polymorphic acetylation; slow acetylators generally have higher plasma levels of hydralazine and require lower doses to maintain control of blood pressure. Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine.

Administration of hydralazine with food results in higher levels of the drug in plasma.

Hydrochlorothiazide: Onset of action of thiazides occurs in 2 hours and the peak effect at about 4 hours. The action persists for approximately 6-12 hours. Hydrochlorothiazide is rapidly absorbed, as indicated by peak concentrations 1-2.5 hours after oral administration. Plasma levels of the drug are proportional to dose; the concentration in whole blood is 1.6-1.8 times higher than in plasma. Thiazides are eliminated rapidly by the kidney. After oral administration of 25 to 100 mg doses, 72-97% of the dose is excreted in the urine, indicating dose-independent absorption. Hydrochlorothiazide is eliminated from plasma in a biphasic fashion with a terminal half-life of 10-17 hours. Plasma protein binding is 67.9%. Plasma clearance is 15.9-30.0 L/hr; volume of distribution is 3.6-7.8 L/kg.

Gastrointestinal absorption of hydrochlorothiazide is enhanced when administered with food. Absorption is decreased in patients with congestive heart failure, and the pharmacokinetics are considerably different in these patients.

Indications and Usage for Hydralazine and Hydrochlorothiazide

Hypertension (see boxed WARNING).

Contraindications

Hydralazine

Hypersensitivity to hydralazine; coronary artery disease; mitral valvular rheumatic heart disease.

Hydrochlorothiazide

Anuria; hypersensitivity to this or other sulfonamide-derived drugs.

Warnings

Hydralazine

In a few patients hydralazine may produce a clinical picture simulating systemic lupus erythematosus including glomerulonephritis. In such patients hydralazine should be discontinued unless the benefit-to-risk determination requires continued antihypertensive therapy with this drug. Signs and symptoms usually regress when the drug is discontinued, but residua have been detected many years later. Long-term treatment with steroids may be necessary. (SeePRECAUTIONS, Laboratory Tests.)

Hydrochlorothiazide

Thiazides should be used with caution in patients with severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte imbalance may precipitate hepatic coma.

Thiazides may add to or potentiate the action of other antihypertensive drugs. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

Sensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.

GENERAL PRECAUTIONS

Hydralazine: Myocardial stimulation produced by hydralazine can cause anginal attacks and ECG changes indicative of myocardial ischemia. The drug has been implicated in the production of myocardial infarction. It must, therefore, be used with caution in patients with suspected coronary artery disease.

The “hyperdynamic” circulation caused by hydralazine may accentuate specific cardiovascular inadequacies. For example, hydralazine may increase pulmonary artery pressure in patients with mitral valvular disease. The drug may reduce the pressor responses to epinephrine. Postural hypotension may result from hydralazine but is less common than with ganglionic blocking agents. It should be used with caution in patients with cerebral vascular accidents.

In hypertensive patients with normal kidneys who are treated with hydralazine, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate. In some instances where control values were below normal, improved renal function has been noted after administration of hydralazine. However, as with any antihypertensive agent, hydralazine should be used with caution in patients with advanced renal damage.

Peripheral neuritis, evidenced by paresthesia, numbness, and tingling, has been observed. Published evidence suggests that hydralazine has an antipyridoxine effect and that pyridoxine should be added to the regimen if symptoms develop.

Hydrochlorothiazide:All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance, namely hyponatremia, hypochloremic alkalosis, and hypokalemia (seeLaboratory TestsandDrug/Drug Interactions). Warning signs are dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbance, such as nausea or vomiting.

Hypokalemia may develop, especially in cases of brisk diuresis or severe cirrhosis.

Interference with adequate oral intake of electrolytes will also contribute to hypokalemia. Hypokalemia may be avoided or treated by the use of potassium supplements or foods with a high potassium content.

Any chloride deficit is generally mild and usually does not require specific treatment, except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In cases of actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Latent diabetes may become manifest during thiazide administration (see Drug/Drug Interactions).

The antihypertensive effects of the drug may be enhanced in the postsympathectomy patient.

If progressive renal impairment becomes evident, withholding or discontinuing diuretic therapy should be considered.

Calcium excretion is decreased by thiazides. Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. The common complications of hyperparathyroidism, such as renal lithiasis, bone resorption and peptic ulceration, have not been seen.

Thiazide diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Information for Patients

Patients should be informed of possible side effects and advised to take the medication regularly and continuously as directed.

Laboratory Tests

Hydralazine:Complete blood counts and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy with hydralazine even though the patient is asymptomatic. These studies are also indicated if the patient develops arthralgia, fever, chest pain, continued malaise, or other unexplained signs or symptoms. A positive antinuclear antibody titer requires that the physician carefully weigh the implications of the test results against the benefits to be derived from antihypertensive therapy with a combination drug containing hydralazine.

Blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura, have been reported. If such abnormalities develop, therapy should be discontinued.

Hydrochlorothiazide: Initial and periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids.

Drug Interactions

Hydralazine:MAO inhibitors should be used with caution in patients receiving hydralazine.

When other potent parenteral antihypertensive drugs, such as diazoxide, are used in combination with hydralazine, patients should be continuously observed for several hours for any excessive fall in blood pressure. Profound hypotensive episodes may occur when diazoxide injections and hydralazine are used concomitantly.

Hydrochlorothiazide: Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

Hypokalemia may develop during concomitant use of steroids or ACTH.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged.

Thiazides may decrease arterial responsiveness to norepinephrine, but not enough to preclude effectiveness of the pressor agent for therapeutic use.

Thiazides may increase the responsiveness to tubocurarine.

Lithium renal clearance is reduced by thiazides, increasing the risk of lithium toxicity.

There have been rare reports in the literature of hemolytic anemia occurring with the concomitant use of hydrochlorothiazide and methyldopa.

Concurrent administration of some nonsteroidal anti-inflammatory agents may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics.

Drug and/or Laboratory Test Interactions

Thiazides may decrease serum levels of protein-bound iodine without signs of thyroid disturbance. Hydralazine HCl and hydrochlorothiazide should be discontinued before tests for parathyroid function are made (seeGeneral, Hydrochlorothiazide, Calcium excretion).

Carcinogenesis and Mutagenesis and Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been conducted with hydralazine HCl and hydrochlorothiazide.

Hydralazine:In a lifetime study in Swiss albino mice, there was a statistically significant increase in the incidence of lung tumors (adenomas and adenocarcinomas) of both male and female mice given hydralazine continuously in their drinking water at a dosage of about 250 mg/kg per day (about 80 times the maximum recommended human dose). In a 2-year carcinogenicity study of rats given hydralazine by gavage at doses of 15, 30, and 60 mg/kg per day (approximately 5 to 20 times the recommended human daily dose), microscopic examination of the liver revealed a small, but statistically significant, increase in benign neoplastic nodules in male and female rats from the high-dose group and in female rats from the intermediate-dose group. Benign interstitial cell tumors of the testes were also significantly increased in male rats from the high-dose group. The tumors observed are common in aged rats, and a significantly increased incidence was not observed until 18 months of treatment. Hydralazine was shown to be mutagenic in bacterial systems (Gene Mutation and DNA Repair) and in one of two rat and one rabbit hepatocytein vitroDNA repair studies. Additionalin vivoandin vitrostudies using lymphoma cells, germinal cells, and fibroblasts from mice, bone marrow cells from Chinese hamsters and fibroblasts from human cell lines did not demonstrate any mutagenic potential for hydralazine.

The extent to which these findings indicate a risk to man is uncertain. While long-term clinical observation has not suggested that human cancer is associated with hydralazine use, epidemiologic studies have so far been insufficient to arrive at any conclusions.

Fertility studies in animals have not been conducted with hydralazine.

Hydrochlorothiazide: Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses up to approximately 600 mg/kg/day) or in male and female rats (at doses up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic inin vitroassays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 ofSalmonella typhimurium(Ames assay) and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or inin vivoassays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and theDrosophilasex-linked recessive lethal trait gene. Positive test results were obtained only in thein vitroCHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 µg/mL, and in theAspergillus nidulansnondisjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses up to 100 and 4 mg/kg/day, respectively, prior to mating, and throughout gestation.

Pregnancy:Teratogenic Effects.Pregnancy Category C

Animal reproduction studies have not been conducted with hydralazine HCl and hydrochlorothiazide.

Hydralazine:Animal studies indicate that hydralazine is teratogenic in mice at 20-30 times the maximum daily human dose of 200-300 mg and possibly in rabbits at 10-15 times the maximum daily human dose, but that it is nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformations of facial and cranial bones.

Hydrochlorothiazide: Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively, provided no evidence of harm to the fetus. There are, however, no adequate and well controlled studies of hydralazine HCl and hydrochlorothiazide in pregnant women. Because animal reproduction studies are not always predictive of human response, this combination drug should be used during pregnancy only if clearly needed.

Nonteratogenic Effects

Hydrochlorothiazide: Thiazides cross the placental barrier and appear in cord blood, and there is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Nursing Mothers

It is not known whether hydralazine is excreted in human milk. Thiazides are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of the combination drug in children have not been established.

Adverse Reactions

Adverse reactions are usually reversible upon reduction of dosage or discontinuation of hydralazine HCl and hydrochlorothiazide. Whenever adverse reactions are moderate or severe, it may be necessary to discontinue the drug.

Hydralazine: The following adverse reactions have been observed, but there has not been enough systematic collection of data to support an estimate of their frequency.

Common

Headache, anorexia, nausea, vomiting, diarrhea, palpitations, tachycardia, angina pectoris.

Less Frequent

Digestive:Constipation, paralytic ileus.

Cardiovascular: Hypotension, paradoxical pressor response, edema.

Respiratory:Dyspnea.

Neurologic: Peripheral neuritis, evidenced by paresthesia, numbness, and tingling; dizziness; tremors; muscle cramps; psychotic reactions characterized by depression, disorientation, or anxiety.

Genitourinary:Difficulty in urination.

Hematologic:Blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, purpura; lymphadenopathy; splenomegaly.

Hypersensitive Reactions: Rash, urticaria, pruritus, fever, chills, arthralgia, eosinophilia, and rarely, hepatitis.

Other:Nasal congestion, flushing, lacrimation, conjunctivitis.

Hydrochlorothiazide:The following adverse reactions have been observed but there has not been enough systematic collection of data to support an estimate of their frequency. Consequently the reactions are categorized by organ systems and are listed in decreasing order of severity and not frequency.

Digestive:Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, anorexia.

Cardiovascular: Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics).

Neurologic: Vertigo, dizziness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, restlessness.

Musculoskeletal: Muscle spasm.

Hematologic:Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Metabolic: Hyperglycemia, glycosuria, hyperuricemia.

Hypersensitive Reactions: Necrotizing angitis, Stevens-Johnson syndrome, respiratory distress including pneumonitis and pulmonary edema, purpura, urticaria, rash, photosensitivity.

Overdosage

Acute Toxicity

Oral LD50’s in rats (mg/kg): hydralazine, 173 and 187; hydrochlorothiazide, 2750.

Signs and Symptoms

Hydralazine: Signs and symptoms of overdosage include hypotension, tachycardia, headache, and generalized skin flushing.

Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac arrhythmia and profound shock.

Hydrochlorothiazide: The most prominent feature of poisoning is acute loss of fluid and electrolytes.

Cardiovascular: Tachycardia, hypotension, shock.

Neuromuscular:Weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness.

Digestive: Nausea, vomiting, thirst.

Renal:Polyuria, oliguria or anuria (due to hemoconcentration).

Laboratory Findings: Hypokalemia, hyponatremia, hypochloremia, alkalosis; increased BUN (especially in patients with renal insufficiency).

Combined Poisoning: Signs and symptoms may be aggravated or modified by concomitant intake of antihypertensive medication, barbiturates, curare, digitalis (hypokalemia), corticosteroids, narcotics, or alcohol.

Treatment

There is no specific antidote.

The gastric contents should be evacuated, taking adequate precautions against aspiration and for protection of the airway. An activated charcoal slurry may be instilled if conditions permit. Dialysis may not be effective for elimination of hydralazine HCl and hydrochlorothiazide because of its plasma protein binding (seeCLINICAL PHARMACOLOGY).

These manipulations may have to be omitted or carried out after cardiovascular status has been stabilized, since they might precipitate cardiac arrhythmias or increase the depth of shock.

Support of the cardiovascular system is of primary importance in suspected hydralazine overdosage. Shock should be treated with plasma expanders. The patient’s legs should be kept raised and lost fluid and electrolytes (potassium, sodium) should be replaced. If possible, vasopressors should not be given, but if a vasopressor is required, care should be taken not to precipitate or aggravate cardiac arrhythmia. Tachycardia responds to beta blockers. Digitalization may be necessary, and renal function should be monitored and supported as required.

Hydralazine and Hydrochlorothiazide Dosage and Administration

Dosage should be determined by individual titration (see boxedWARNING).

The usual dosage is one hydralazine HCl and hydrochlorothiazide capsule twice daily, the strength depending upon individual requirement following titration. For maintenance, the dosage should be adjusted to the lowest effective level.

When necessary, other antihypertensive agents such as sympathetic inhibitors may be added gradually in reduced dosages, and the effects should be watched carefully.

How is Hydralazine and Hydrochlorothiazide Supplied

Hydralazine HCl and hydrochlorothiazide are supplied as two piece hard gelatin capsules, in three dosage strengths:

25 mg hydralazine hydrochloride and 25 mg hydrochlorothiazide capsules are white and imprinted “Par 143”, and are available in bottles of 100 (NDC #49884-143-01), 500 (NDC #49884-143-05) and 1000 (NDC #49884-143-10).

50 mg hydralazine hydrochloride and 50 mg hydrochlorothiazide capsules are white/black and imprinted “Par 144”, and are available in bottles of 100 (NDC #49884-144-01), 500 (NDC #49884-144-05) and 1000 (NDC #49884-144-10).

100 mg hydralazine hydrochloride and 50 mg hydrochlorothiazide capsules are powder blue/light blue and imprinted “Par 145”, and are available in bottles of 100 (NDC #49884-145-01), 500 (NDC #49884-145-05) and 1000 (NDC #49884-145-10).

Store at controlled room temperature 15°-30°C (59°-86°F).

Dispense in a tight, light-resistant container as defined in the USP.

Manufactured by:

PAR PHARMACEUTICAL, INC.

Spring Valley, NY 10977

Revised: 03/05. OS143-01-1-15

PRINCIPAL DISPLAY PANEL – 25MG/25MG 100 CAPSULES

PRINCIPAL DISPLAY PANEL 25MG/25MG 500 CAPSULES

PRINCIPAL DISPLAY PANEL 50MG/50MG 100 CAPSULES

HYDRALAZINE HCL AND HYDROCHLOROTHIAZIDE  hydralazine hydrochloride and hydrochlorothiazide  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 49884-143 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HYDRALAZINE HYDROCHLORIDE (HYDRALAZINE) HYDRALAZINE HYDROCHLORIDE 25 mg HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZIDE) HYDROCHLOROTHIAZIDE 25 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color WHITE Score no score Shape CAPSULE Size 16mm Flavor Imprint Code Par;143 Contains

Packaging # NDC Package Description Multilevel Packaging 1 49884-143-01 100 CAPSULE In 1 BOTTLE None 2 49884-143-05 500 CAPSULE In 1 BOTTLE None 3 49884-143-10 1000 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA088957	10/21/1985	10/29/2009

HYDRALAZINE HCL AND HYDROCHLOROTHIAZIDE  hydralazine hydrochloride and hydrochlorothiazide  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 49884-144 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HYDRALAZINE HYDROCHLORIDE (HYDRALAZINE) HYDRALAZINE HYDROCHLORIDE 50 mg HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZIDE) HYDROCHLOROTHIAZIDE 50 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color WHITE (White) , BLACK (Black) Score no score Shape CAPSULE Size 18mm Flavor Imprint Code Par;144 Contains

Packaging # NDC Package Description Multilevel Packaging 1 49884-144-01 100 CAPSULE In 1 BOTTLE None 2 49884-144-05 500 CAPSULE In 1 BOTTLE None 3 49884-144-10 1000 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA088946	10/21/1985	10/29/2009

HYDRALAZINE HCL AND HYDROCHLOROTHIAZIDE  hydralazine hydrochloride and hydrochlorothiazide  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 49884-145 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HYDRALAZINE HYDROCHLORIDE (HYDRALAZINE) HYDRALAZINE HYDROCHLORIDE 100 mg HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZIDE) HYDROCHLOROTHIAZIDE 50 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BLUE Score no score Shape CAPSULE Size 19mm Flavor Imprint Code Par;145 Contains

Packaging # NDC Package Description Multilevel Packaging 1 49884-145-01 100 CAPSULE In 1 BOTTLE None 2 49884-145-05 500 CAPSULE In 1 BOTTLE None 3 49884-145-10 1000 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA088961	10/21/1985	10/29/2009

Labeler - Par Pharmaceutical, Inc. (092733690)

Registrant - Par Pharmaceutical, Inc. (092733690)

Revised: 10/2009Par Pharmaceutical, Inc.

More Hydralazine and Hydrochlorothiazide resources

• Hydralazine and Hydrochlorothiazide Side Effects (in more detail)
• Hydralazine and Hydrochlorothiazide Dosage
• Hydralazine and Hydrochlorothiazide Use in Pregnancy & Breastfeeding
• Drug Images
• Hydralazine and Hydrochlorothiazide Drug Interactions
• Hydralazine and Hydrochlorothiazide Support Group
• 0 Reviews for Hydralazine and Hydrochlorothiazide - Add your own review/rating

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Horse Chestnut Controlled-Release Capsules

Pronunciation: Not applicable.
Generic Name: Horse Chestnut
Brand Name: Generics only. No brands available.

Horse Chestnut Controlled-Release Capsules are used for:

Swelling and pain due to varicose veins. It has also been used for the inflammation of hemorrhoids and veins. It may have other uses as well. Check with your pharmacist for more details regarding the particular brand you use.

Horse Chestnut Controlled-Release Capsules are an herbal product. It works by reducing swelling and improving blood flow.

Do NOT use Horse Chestnut Controlled-Release Capsules if:

• you are allergic to any ingredient in Horse Chestnut Controlled-Release Capsules


• you have a history of kidney or liver problems


• you have a stomach or bowel infection or irritation


• you are pregnant or breast-feeding

Contact your doctor or health care provider right away if any of these apply to you.

Before using Horse Chestnut Controlled-Release Capsules:

Some medical conditions may interact with Horse Chestnut Controlled-Release Capsules. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are planning to become pregnant


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances

Some MEDICINES MAY INTERACT with Horse Chestnut Controlled-Release Capsules. However, no specific interactions are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Horse Chestnut Controlled-Release Capsules 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.

How to use Horse Chestnut Controlled-Release Capsules:

Use Horse Chestnut Controlled-Release Capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Dosing depends on the use and the source of the product.


• Use as directed on the package, unless instructed otherwise by your doctor.


• Check product labeling carefully. Horse chestnut seed extract is different than whole horse chestnut seeds. Do not use whole horse chestnut seeds. Whole horse chestnut seeds are poisonous.


• Swallow whole. Do not break, crush, or chew before swallowing.


• If you miss taking a dose of Horse Chestnut Controlled-Release Capsules for 1 or more days, there is no cause for concern. If your doctor recommended that you take it, try to remember your dose every day.

Ask your health care provider any questions you may have about how to use Horse Chestnut Controlled-Release Capsules.

Important safety information:

• This product has not been approved by the Food and Drug Administration (FDA) as safe and effective for any medical condition. The long-term safety of herbal products is not known. Before using any alternative medicine, talk with your doctor or pharmacist.


• Keep all doctor and lab appointments while you are using this product.


• Horse chestnut may color your urine red. This is harmless.


• This product is not recommended for use in CHILDREN.


• PREGNANCY and BREAST-FEEDING: Do not use this product if you are pregnant unless clearly needed. Do not breast-feed while using this product.

Possible side effects of Horse Chestnut Controlled-Release Capsules:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dizziness; nausea; stomach irritation; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); fatigue; fever; 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.

See also: Horse Chestnut side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms of poisoning from whole horse chestnut seeds include diarrhea; dilated pupils; muscle twitching; paralysis; stupor; vomiting.

Proper storage of Horse Chestnut Controlled-Release Capsules:

Store at room temperature away from heat, moisture, and light unless otherwise directed on the package label. Do not store in the bathroom. Most herbal products are not in childproof containers. Keep Horse Chestnut Controlled-Release Capsules out of the reach of children and away from pets.

General information:

• If you have any questions about Horse Chestnut Controlled-Release Capsules, please talk with your doctor, pharmacist, or other health care provider.


• Horse Chestnut Controlled-Release Capsules are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Horse Chestnut Controlled-Release Capsules. 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.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Horse Chestnut resources

• Horse Chestnut Side Effects (in more detail)
• Horse Chestnut Use in Pregnancy & Breastfeeding
• Horse Chestnut Drug Interactions
• Horse Chestnut Support Group
• 2 Reviews for Horse Chestnut - Add your own review/rating

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• Inflammatory Conditions
• Nocturnal Leg Cramps
• Varicose Veins

Timolol Gel Eye Drops

Pronunciation: TIM-oh-lol
Generic Name: Timolol
Brand Name: Timoptic XE

Timolol Gel Eye Drops are used for:

Treating increased pressure in the eye (ocular hypertension) and open-angle glaucoma. It may also be used for other conditions as determined by your doctor.

Timolol Gel Eye Drops are a beta-blocker. It works to decrease fluid production and pressure inside the eye.

Do NOT use Timolol Gel Eye Drops if:

• you are allergic to any ingredient in Timolol Gel Eye Drops


• you have severe chronic obstructive pulmonary disease (COPD) or a history of asthma


• you have heart block, heart failure, or an unusually slow heartbeat


• you are in shock caused by severe heart problems


• you are using another beta-blocker eye drop (eg, betaxolol)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Timolol Gel Eye Drops:

Some medical conditions may interact with Timolol Gel Eye Drops. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of lung or breathing problems (eg, bronchitis, COPD, emphysema), diabetes, low blood sugar, heart problems, certain muscle problems (eg, myasthenia gravis, muscle weakness), blood vessel problems, or an overactive thyroid


• if you have narrow-angle glaucoma, double vision, a drooping eyelid, or an eye infection or injury

Some MEDICINES MAY INTERACT with Timolol Gel Eye Drops. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Bupivacaine, calcium channel blockers (eg, verapamil), certain antiarrhythmics (eg, disopyramide, flecainide, quinidine), cimetidine, digoxin, ketanserin, reserpine, or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because serious heart problems (eg, conduction problems, heart failure, slow heartbeat) or low blood pressure may occur


• Clonidine because increased blood pressure may occur


• Insulin or oral antidiabetics (eg, glyburide, repaglinide) because the risk of low blood sugar (eg, dizziness, headache, hunger, shakiness or weakness, sweating) or slow heart rate may be increased. Timolol Gel Eye Drops may also hide certain signs of low blood sugar


• Alpha-blockers (eg, alfuzosin, prazosin), oral beta-blockers (eg, propranolol), or other beta-blocker eye drops (eg, betaxolol) because the risk of their side effects may be increased by Timolol Gel Eye Drops


• Certain sympathomimetics (eg, albuterol, salmeterol), epinephrine, or theophylline because their effectiveness may be decreased by Timolol Gel Eye Drops

This may not be a complete list of all interactions that may occur. Ask your health care provider if Timolol Gel Eye Drops may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Timolol Gel Eye Drops:

Use Timolol Gel Eye Drops as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Timolol Gel Eye Drops. Talk to your pharmacist if you have questions about this information.


• Timolol Gel Eye Drops are only for the eye. Do not get it in your nose or mouth.


• Soft contact lenses may absorb a chemical in Timolol Gel Eye Drops. Remove contact lenses before you use Timolol Gel Eye Drops; lenses may be placed back in the eyes 15 minutes after use of Timolol Gel Eye Drops.


• Turn the closed bottle upside down and shake once before each use.


• To use Timolol Gel Eye Drops in the eye, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eye for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean, dry tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.


• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.


• Do NOT overtighten the cap on the bottle. This may damage the bottle or cap.


• Do NOT try to make the hole of the medicine dropper larger.


• Use Timolol Gel Eye Drops at least 10 minutes before or after any other medicine that you put in your eye.


• Using Timolol Gel Eye Drops at the same time each day will help you remember to use it.


• Continue to use Timolol Gel Eye Drops even if you feel well. Do not miss any doses.


• If you miss a dose of Timolol Gel Eye Drops, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Timolol Gel Eye Drops.

Important safety information:

• Timolol Gel Eye Drops may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Timolol Gel Eye Drops with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Tell your doctor or dentist that you take Timolol Gel Eye Drops before you receive any medical or dental care, emergency care, or surgery.


• Contact your doctor if you have an eye injury or infection, or if you will be having eye surgery.


• Diabetes patients - Timolol Gel Eye Drops may hide signs of low blood sugar, such as a rapid heartbeat. Be sure to watch for other signs of low blood sugar. Low blood sugar may make you anxious, sweaty, weak, dizzy, drowsy, or faint. It may also make your vision change; give you a headache, chills, or tremors; or make you more hungry. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• If you have a history of any severe allergic reaction, talk with your doctor. You may be at risk for an even more severe allergic reaction if you come into contact with the substance that caused your allergy. Some medicines used to treat severe allergies may also not work as well while you are using Timolol Gel Eye Drops.


• Timolol Gel Eye Drops may cause harm if it is swallowed. If you may have taken it by mouth, contact your poison control center or emergency room right away.


• Lab tests, including eye pressure, may be performed while you use Timolol Gel Eye Drops. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Timolol Gel Eye Drops should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Timolol Gel Eye Drops while you are pregnant. Timolol Gel Eye Drops are found in breast milk. Do not breast-feed while taking Timolol Gel Eye Drops.

Possible side effects of Timolol Gel Eye Drops:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Blurred vision; dizziness; dry eyes; feeling that something is in your eye; headache; increased tear production; minor burning, itching, or stinging of the eye; nausea.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain or discomfort; confusion; eye irritation, swelling, pain, or discharge; eyelid pain, redness, scaling, drooping, or swelling; fainting; pain, numbness, weakness, or tingling of an arm or leg; severe or persistent headache or dizziness; shortness of breath; slow or irregular heartbeat; swelling of the hands, ankles, or feet; vision changes.

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.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include chest pain; difficulty breathing or shortness of breath; severe or persistent dizziness or headache; slow or irregular heartbeat.

Proper storage of Timolol Gel Eye Drops:

Store some brands of Timolol Gel Eye Drops at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Some brands should be stored between 36 and 77 degrees F (2 and 25 degrees C). Check with your pharmacist to see how to store your brand of Timolol Gel Eye Drops. Protect from freezing. Store away from heat, moisture, and light. Keep Timolol Gel Eye Drops out of the reach of children and away from pets.

General information:

• If you have any questions about Timolol Gel Eye Drops, please talk with your doctor, pharmacist, or other health care provider.


• Timolol Gel Eye Drops are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Timolol Gel Eye Drops. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Timolol resources

• Timolol Use in Pregnancy & Breastfeeding
• Timolol Drug Interactions
• Timolol Support Group
• 1 Review for Timolol - Add your own review/rating

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Histex SR

Generic Name: brompheniramine and pseudoephedrine (BROM fen EER a meen and SOO doe ed FED rin)

Brand Names: Andehist NR Syrup, Bidhist-D, Bromaline, Bromhist Pediatric Drops, Bromhist-NR, BroveX PD, BroveX PSE, Brovex SR, Di-Bromm, Histex SR, J-TanD PD, Lodrane 12D, Lodrane 24D, Lodrane D, Lodrane Liquid, LoHist-12D, LoHist-PD, Q-Tapp, Sildec, Touro Allergy, Ultrabrom, Ultrabrom PD

What is Histex SR (brompheniramine and pseudoephedrine)?

Brompheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of brompheniramine and pseudoephedrine is used to treat sneezing, cough, runny or stuffy nose, itchy or watery eyes, hives, skin rash, itching, and other symptoms of allergies and the common cold.

Brompheniramine and pseudoephedrine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Histex SR (brompheniramine and pseudoephedrine)?

There are many brands and forms of this medicine available and not all brands are listed on this leaflet.

Do not give this medication to a child younger than 2 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use any other over-the-counter cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains an antihistamine or decongestant. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body. Brompheniramine and pseudoephedrine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

What should I discuss with my healthcare provider before taking Histex SR (brompheniramine and pseudoephedrine)?

Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Ask a doctor or pharmacist if it is safe for you to take brompheniramine and pseudoephedrine if you have:

• kidney disease;


• 
  

  diabetes;

  
  


• 
  

  glaucoma;

  
  


• 
  

  heart disease or high blood pressure;

  
  


• 
  

  diabetes;

  
  


• 
  

  a thyroid disorder;

  
  


• 
  

  an enlarged prostate; or

  
  


• 
  

  problems with urination.

  
  

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Brompheniramine and pseudoephedrine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take Histex SR (brompheniramine and pseudoephedrine)?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts, or use it for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 2 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Take this medicine with a full glass of water. Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking or opening the pill would cause too much of the drug to be released at one time.

Measure the liquid form of this medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

If you need to have any type of surgery, tell the surgeon ahead of time if you have taken a cold medicine within the past few days.

This medication can cause you to have unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

Store the medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cold or allergy medicine is usually taken only as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include feeling restless or nervous, nausea, vomiting, stomach pain, dizziness, drowsiness, dry mouth, warmth or tingly feeling, or seizure (convulsions).

What should I avoid while taking Histex SR (brompheniramine and pseudoephedrine)?

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Do not use any other over-the-counter cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains an antihistamine or decongestant.

Histex SR (brompheniramine and pseudoephedrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

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  fast, pounding, or uneven heartbeat;

  
  


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  confusion, hallucinations, unusual thoughts or behavior;

  
  


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  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


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  increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);

  
  


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  confusion, hallucinations, unusual thoughts or behavior;

  
  


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  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms; or

  
  


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  urinating less than usual or not at all.

  
  

Less serious side effects may include:

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  blurred vision;

  
  


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  dry mouth;

  
  


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  nausea, stomach pain, constipation;

  
  


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  mild loss of appetite, stomach upset;

  
  


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  warmth, tingling, or redness under your skin;

  
  


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  sleep problems (insomnia);

  
  


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  restless or excitability (especially in children);

  
  


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  skin rash or itching;

  
  


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  dizziness, drowsiness;

  
  


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  problems with memory or concentration; or

  
  


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  ringing in your ears.

  
  

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.

What other drugs will affect Histex SR (brompheniramine and pseudoephedrine)?

Sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by brompheniramine. Tell your doctor if you regularly use any of these medicines, or any other cold or allergy medications..

Tell your doctor about all other medications you use, especially:

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  medicines to treat high blood pressure;

  
  


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  a diuretic (water pill);

  
  


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  medication to treat irritable bowel syndrome;

  
  


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  bladder or urinary medications such as oxybutynin (Ditropan, Oxytrol) or tolterodine (Detrol);

  
  


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  aspirin or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others);

  
  


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  a beta-blocker such as atenolol (Tenormin), carteolol (Cartrol), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal), sotalol (Betapace), timolol (Blocadren), and others; or

  
  


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  antidepressants such as amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Janimine, Tofranil), and others.

  
  

This list is not complete and there may be other drugs that can interact with brompheniramine and pseudoephedrine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Histex SR resources

• Histex SR Side Effects (in more detail)
• Histex SR Use in Pregnancy & Breastfeeding
• Drug Images
• Histex SR Drug Interactions
• Histex SR Support Group
• 0 Reviews for Histex SR - Add your own review/rating

• Histex SR Controlled-Release and Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Bidhist-D Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Lodrane D MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Histex SR with other medications

• Hay Fever
• Nasal Congestion

Where can I get more information?

• Your pharmacist can provide more information about brompheniramine and pseudoephedrine.

See also: Histex SR side effects (in more detail)