Inderide

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• other beta blockers such as metoprolol (Toprol XL, Lopressor), carvedilol (Coreg), bisoprolol (Zebeta), betaxolol (Kerlone), and nebivolol (Bystolic)
• drugs that deplete a substance in the body called catecholamines such as reserpine (Serpalan) or guanethidine (Ismelin)
• medications that slow the heart or help treat abnormal heart rhythms such as verapamil (Calan), diltiazem (Cardizem), digoxin (Lanoxicaps, Lanoxin), and digitoxin 
• nonsteroidal anti-inflammatory drugs (NSAIDS) such as naproxen (Aleve) and ibuprofen (Advil)
• haloperidol (Haldol)
• aluminum hydroxide gel
• phenytoin (Dilantin), rifampin
• chlorpromazine (Thorazine)
• antipyrine and lidocaine
• thyroxine
• cimetidine (Tagamet)
• theophylline (Theolair)
• norepinephrine (Levophed)
• tubocurarine
• medicines that provide relief for inflamed areas of the body (corticosteroids) such as methylprednisolone (Medrol) and dexamethasone (Decadron)

Do not drink alcohol while taking Inderide. 

This is not a complete list of Inderide drug interactions. Ask your doctor or pharmacist for more information. 

If you take too much Inderide, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away. 

You should not use this medicine if you have asthma or if you are unable to urinate. You should not use hydrochlorothiazide and propranolol if you have a serious heart condition such as "sick sinus syndrome" or "AV block," severe heart failure, or slow heartbeats that have caused you to faint.

Propranolol and hydrochlorothiazide combination is used to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Propranolol is a beta-blocker. It works by affecting the response to some nerve impulses in certain parts of the body, like the heart. As a result, the heart beats slower and decreases the blood pressure. When the blood pressure is lowered, the amount of blood and oxygen is increased to the heart.

Hydrochlorothiazide is a diuretic (water pill). It reduces the amount of water in the body by increasing the flow of urine, which helps lower the blood pressure.

This medicine is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

This medicine may cause serious allergic reactions including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash; itching; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, lips, tongue, or throat while you are using this medicine.

This medicine may cause heart failure in some patients. Check with your doctor right away if you are having chest pain or discomfort; dilated neck veins; extreme fatigue; irregular breathing; an irregular heartbeat; shortness of breath; swelling of the face, fingers, feet, or lower legs; weight gain; or wheezing.

Do not interrupt or stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. Some conditions may become worse when the medicine is stopped suddenly, which can be dangerous.

This medicine may cause changes in your blood sugar levels. Also, this medicine may cover up signs of low blood sugar, such as a rapid pulse rate. Check with your doctor if you have these problems or if you notice a change in the results of your blood or urine sugar tests.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.

Serious skin reactions can occur during treatment with this medicine. Check with your doctor right away if you start having skin itching, swelling, rash, or redness; blistering, peeling, or loosening of the skin; or any other unusual effects that may be caused by this medicine.

Check with your doctor right away if you start having dry mouth, increased thirst, muscle cramps, nausea or vomiting, unusual tiredness or weakness, severe drowsiness or dizziness, seizures, a decrease in urine, or a fast heartbeat while you are using this medicine. These may be symptoms of dehydration or mineral imbalance.

Stop using this medicine and check with your doctor immediately if blurred vision, difficulty in reading, eye pain, or any other change in vision occurs during or after treatment. This could be a sign of a serious eye problem. Your doctor will want you to have your eyes checked by an ophthalmologist (eye doctor).

Do not take other medicines unless they have been discussed with your doctor. This especially includes prescription or nonprescription (over-the-counter) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, since they may increase your blood pressure.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abdominal or stomach pain, usually after eating a meal
• abdominal or stomach tenderness
• black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of the skin
• bloating
• blood in the urine
• bloody nose
• bloody stools
• blurred or loss of vision
• body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain or discomfort
• clay-colored stools
• cold sweats
• confusion about identity, place, and time
• congestion
• constipation
• cough
• coughing up blood
• cracks in the skin
• crying
• darkened urine
• decreased awareness or responsiveness
• decreased urine output
• depersonalization
• diarrhea
• difficulty with breathing or swallowing
• dilated neck veins
• disturbed color perception
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• double vision
• dry mouth
• dryness or soreness of the throat
• dysphoria
• euphoria
• extreme fatigue
• fast, pounding, slow, or irregular heartbeat
• fever or chills
• flushing or redness of the skin
• fruit-like breath odor
• general feeling of discomfort or illness
• general feeling of tiredness or weakness
• hair loss
• halos around lights
• headaches
• heavier menstrual periods
• hives or welts
• hoarseness
• increased hunger
• increased sensitivity of the skin to sunlight
• increased thirst
• increased urination
• indigestion
• irregular breathing
• irregular heartbeat
• itching
• joint pain, stiffness, or swelling
• lightheadedness, dizziness, or fainting
• loss of appetite
• loss of heat from the body
• loss of strength or energy
• lower back or side pain
• mental depression
• mimicry of speech or movements
• muscle pain or weakness
• mutism
• nausea or vomiting
• negativism
• night blindness
• noisy breathing
• overbright appearance of lights
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• paleness or cold feeling in the fingertips and toes
• paranoia
• peculiar postures or movements, mannerisms or grimacing
• pinpoint red or purple spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• quick to react or overreact emotionally
• rapidly changing moods
• rectal bleeding
• red skin lesions, often with a purple center
• red, irritated eyes
• red, swollen skin
• reddening of the skin, especially around the ears
• runny nose
• scaly skin
• seeing, hearing, or feeling things that are not there
• severe sleepiness
• severe sunburn
• short-term memory loss
• shortness of breath
• skin irritation or rash, including rash that looks like psoriasis
• sleeplessness
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• sugar in the urine
• sweating
• swelling of the eyes, face, or inside of the nose
• swelling of the fingers, feet, or lower legs
• tender, swollen, or painful glands in the neck
• tenderness of salivary glands
• tenderness, burning, or peeling of the skin
• thickening of bronchial secretions
• tightness in the chest
• tingling or pain in the fingers or toes when exposed to cold
• trouble with sleeping
• trouble with swallowing
• troubled breathing
• tunnel vision
• unable to sleep
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight loss
• unusually warm skin
• voice changes
• vomiting of blood
• weight gain
• wheezing
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Change in consciousness
• decreased urination
• fast, slow, or shallow breathing
• gas
• heartburn
• increase in heart rate
• increased sweating
• indigestion
• loss of consciousness
• low blood pressure
• muscle cramps
• pale or blue lips, fingernails, or skin
• rapid breathing
• seizures
• sunken eyes
• unusual drowsiness, dullness, or feeling of sluggishness
• unusual paleness
• weakness and heaviness of the legs
• wrinkled skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decreased interest in sexual intercourse
• dry eyes
• feeling of constant movement of self or surroundings
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• muscle spasm
• pain of the penis on erection
• pain or discomfort in the chest, upper stomach, or throat
• restlessness
• sensation of spinning
• stomach cramps
• thinning of the hair
• vivid dreams

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Propranolol hydrochloride (Inderal®)

Propranolol is contraindicated in 1) cardiogenic shock; 2) sinus bradycardia and greater than first-degree block; 3) bronchial asthma; 4) congestive heart failure (see “WARNINGS”) unless the failure is secondary to a tachyarrhythmia treatable with propranolol.

Hydrochlorothiazide

Hydrochlorothiazide is contraindicated in patients with anuria or hypersensitivity to this or other sulfonamide-derived drugs.

Propranolol hydrochloride (Inderal®)

Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been associated with the administration of propranolol (see “ADVERSE REACTIONS”).

Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure, and inhibition with beta blockade always carries the potential hazard of further depressing myocardial contractility and precipitating cardiac failure. Propranolol acts selectively without abolishing the inotropic action of digitalis on the heart muscle (i.e., that of supporting the strength of myocardial contractions). In patients already receiving digitalis, the positive inotropic action of digitalis may be reduced by propranolol's negative inotropic effect.

Patients Without a History of Heart Failure: Continued depression of the myocardium over a period of time can, in some cases, lead to cardiac failure. In rare instances, this has been observed during propranolol therapy. Therefore, at the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or given additional diuretic, and the response observed closely: a) if cardiac failure continues, despite adequate digitalization and diuretic therapy, propranolol therapy should be withdrawn (gradually, if possible); b) if tachyarrhythmia is being controlled, patients should be maintained on combined therapy and the patient closely followed until threat of cardiac failure is over.

Angina Pectoris: There have been reports of exacerbation of angina and, in some cases, myocardial infarction following abrupt discontinuation of propranolol therapy. Therefore, when discontinuance of propranolol is planned, the dosage should be gradually reduced and the patient should be carefully monitored. In addition, when propranolol is prescribed for angina pectoris, the patient should be cautioned against interruption or cessation of therapy without the physician's advice. If propranolol therapy is interrupted and exacerbation of angina occurs, it usually is advisable to reinstitute propranolol therapy and take other measures appropriate for the management of unstable angina pectoris. Since coronary artery disease may be unrecognized, it may be prudent to follow the above advice in patients considered at risk of having occult atherosclerotic heart disease, who are given propranolol for other indications.

Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema): PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA BLOCKERS. Propranolol should be administered with caution since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta receptors.

Major Surgery: The necessity or desirability of withdrawal of beta-blocking therapy prior to major surgery is controversial. It should be noted, however, that the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Propranolol, like other beta blockers, is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Difficulty in starting and maintaining the heartbeat has also been reported with beta blockers.

Diabetes and Hypoglycemia: Beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia in labile insulin-dependent diabetes. In these patients, it may be more difficult to adjust the dosage of insulin. Hypoglycemic attack may be accompanied by a precipitous elevation of blood pressure in patients on propranolol.

Propranolol therapy, particularly in infants and children, diabetic or not, has been associated with hypoglycemia especially during fasting as in preparation for surgery. Hypoglycemia also has been found after this type of drug therapy and prolonged physical exertion and has occurred in renal insufficiency, both during dialysis and sporadically, in patients on propranolol.

Acute increases in blood pressure have occurred after insulin-induced hypoglycemia in patients on propranolol.

Thyrotoxicosis: Beta blockade may mask certain clinical signs of hyperthyroidism. Therefore, abrupt withdrawal of propranolol may be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Propranolol may change thyroid-function tests, increasing T4 and reverse T3, and decreasing T3.

Wolff-Parkinson-White Syndrome: Several cases have been reported in which, after propranolol, the tachycardia was replaced by a severe bradycardia requiring a demand pacemaker. In one case this resulted after an initial dose of 5 mg propranolol.

Skin Reactions: Cutaneous reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, and urticaria, have been reported with use of propranolol (see “ADVERSE REACTIONS”).

Hydrochlorothiazide

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

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

Propranolol should be used with caution in patients with impaired hepatic or renal function. Inderide is not indicated for the treatment of hypertensive emergencies.

Risk of anaphylacticreaction. While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance, namely hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Medication such as digitalis may also influence serum electrolytes. Warning signs, irrespective of cause, are: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Hypokalemia may develop, especially with brisk diuresis or when severe cirrhosis is present.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

Hypokalemia may be avoided or treated by 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 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 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.

Diabetes mellitus which has been latent may become manifest during thiazide administration.

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

If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.

Calcium excretion is decreased by thiazides. Pathologic 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.

Information for Patients

Beta-adrenoreceptor blockade can cause reduction of intraocular pressure. Patients should be told that Inderide may interfere with the glaucoma screening test. Withdrawal may lead to a return of increased intraocular pressure.

Laboratory Tests

Elevated blood urea levels in patients with severe heart disease, elevated serum transaminase, alkaline phosphatase, lactate dehydrogenase.

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Drug/Drug Interactions

Patients receiving catecholamine-depleting drugs such as reserpine should be closely observed if Inderide is administered. The added catecholamine-blocking action may produce an excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension.

Caution should be exercised when patients receiving a beta blocker are administered a calcium-channel blocking drug, especially intravenous verapamil, for both agents may depress myocardial contractility or atrioventricular conduction. On rare occasions, the concomitant intravenous use of a beta blocker and verapamil has resulted in serious adverse reactions, especially in patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported.

Hypotension and cardiac arrest have been reported with the concomitant use of propranolol and haloperidol.

Aluminum hydroxide gel greatly reduces intestinal absorption of propranolol.

Alcohol, when used concomitantly with propranolol, may increase plasma levels of propranolol.

Phenytoin, phenobarbitone, and rifampin accelerate propranolol clearance.

Chlorpromazine, when used concomitantly with propranolol, results in increased plasma levels of both drugs.

Antipyrine and lidocaine have reduced clearance when used concomitantly with propranolol.

Thyroxine may result in a lower than expected T3 concentration when used concomitantly with propranolol.

Cimetidine decreases the hepatic metabolism of propranolol, delaying elimination and increasing blood levels.

Theophylline clearance is reduced when used concomitantly with propranolol.

Thiazide drugs may increase the responsiveness to tubocurarine.

Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

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

Hypokalemia may develop during concomitant use of corticosteroids or ACTH.

Drug/Laboratory Test Interactions

Thiazides may decrease serum PBI levels without signs of thyroid disturbance.

Thiazides should be discontinued before carrying out tests for parathyroid function (see “PRECAUTIONSGeneral”).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Combinations of propranolol and hydrochlorothiazide have not been evaluated for carcinogenic or mutagenic potential or for potential to adversely affect fertility.

In dietary administration studies in which mice and rats were treated with propranolol for up to 18 months at doses of up to 150 mg/kg/day, there was no evidence of drug-related tumorigenesis. In a study in which both male and female rats were exposed to propranolol in their diets at concentrations of up to 0.05%, from 60 days prior to mating and throughout pregnancy and lactation for two generations, there were no effects on fertility. Based on differing results from Ames Tests performed by different laboratories, there is equivocal evidence for a genotoxic effect of propranolol in bacteria (S.typhimurium strain TA 1538).

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 of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro in the Ames bacterial mutagen assay (S.typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538) or in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. Nor was it genotoxic in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity), Mouse Lymphoma Cell (mutagenicity) and Aspergillus nidulans non-disjunction assays.

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 of up to 100 mg/kg and 4 mg/kg, respectively, prior to mating and throughout gestation.

Pregnancy: Pregnancy Category C

Combinations of propranolol and hydrochlorothiazide have not been evaluated for effects on pregnancy in animals. Nor are there adequate and well-controlled studies of propranolol, hydrochlorothiazide, or Inderide in pregnant women. Inderide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In a series of reproduction and developmental toxicology studies, propranolol was given to rats by gavage or in the diet throughout pregnancy and lactation. At doses of 150 mg/kg/day (>30 times the dose of propranolol contained in the maximum recommended human daily dose of Inderide), but not at doses of 80 mg/kg/day, treatment was associated with embryotoxicity (reduced litter size and increased resorption sites) as well as neonatal toxicity (deaths). Propranolol also was administered (in the feed) to rabbits (throughout pregnancy and lactation) at doses as high as 150 mg/kg/day (>45 times the dose of propranolol contained in the maximum recommended daily human dose of Inderide). No evidence of embryo or neonatal toxicity was noted.

Intrauterine growth retardation, small placentas, and congenital abnormalities have been reported in human neonates whose mothers received propranolol during pregnancy. Neonates whose mothers received propranolol at parturition have exhibited bradycardia, hypoglycemia and/or respiratory depression. Adequate facilities for monitoring these infants at birth should be available.

Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats at doses of up to 3000 and 1000 mg/kg/day, respectively, provided no evidence of harm to the fetus.

Thiazides cross the placental barrier and appear in cord blood. The use of thiazides in pregnant women requires that the anticipated benefit be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in the adult.

Nursing Mothers

Propranolol is excreted in human milk. Caution should be exercised when Inderide is administered to a nursing woman.

Thiazides appear in breast milk. If the use of drug is deemed essential, the patient should stop nursing.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Inderide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

The dosage must be determined by individual titration.

Hydrochlorothiazide can be given at doses of 12.5 to 50 mg per day when used alone. The initial dose of propranolol is 80 mg daily, and it may be increased gradually until optimal blood pressure control is achieved. The usual effective dose when used alone is 160 to 480 mg per day.

One Inderide Tablet twice daily can be used to administer up to 160 mg of propranolol and 50 mg of hydrochlorothiazide. For doses of propranolol greater than 160 mg the combination products are not appropriate, because their use would lead to an excessive dose of the thiazide component.

When necessary, another antihypertensive agent may be added gradually beginning with 50 percent of the usual recommended starting dose to avoid an excessive fall in blood pressure.