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Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Side Effects


TIMOLIDE (timolol maleate-hydrochlorothiazide) is usually well tolerated in properly selected patients. Most adverse effects have been mild and transient.

The adverse reactions listed in the following table were spontaneously reported and have been arranged into two groups: (1) incidence greater than 1%; and (2) incidence less than 1%. The incidence was obtained from clinical studies conducted in the United States (257 patients treated with TIMOLIDE (timolol maleate-hydrochlorothiazide) ).

Incidence Greater Than 1%

Incidence Less Than 1%



fatigue/tiredness (1.9%)

chest pain

asthenia (1.9%)




hypotension (1.6%)


bradycardia (1.2%)



cardiac failure










gastrointestinal pain












dry mucous









dizziness (1.2%)







decreased libido






trouble concentrating





bronchial spasm (1.6%)


dyspnea (1.2%)





renal colic

The following additional adverse effects have been reported in clinical experience with the drug: cerebral ischemia, cerebral vascular accident, gout, muscle cramps, oculogyric crisis, worsening of chronic obstructive pulmonary disease, earache, and impotence.

Other adverse reactions that have been reported with the individual components are listed below:

Timolol Maleate _ Body as a Whole: extremity pain, decreased exercise tolerance, weight loss, fever; Cardiovascular: cardiac arrest, cerebral vascular accident, worsening of angina pectoris, sinoatrial block, AV block, worsening of arterial insufficiency, Raynaud†s phenomenon, claudication, palpitations, vasodilatation, cold hands and feet, edema; Digestive: hepatomegaly, elevated liver function tests, vomiting; Hematologic: nonthrombocytopenic purpura; Endocrine: hyperglycemia, hypoglycemia; Skin: skin irritation, pruritus, sweating, alopecia; Musculoskeletal: arthralgia; Nervous System: local weakness, vertigo, paresthesia, increase in signs and symptoms of myasthenia gravis; Psychiatric: depression, nightmares, hallucinations; Respiratory: cough; Special Senses: visual disturbances, diplopia, ptosis, eye irritation, dry eyes, tinnitus; Urogenital: urination difficulties.

There have been reports of retroperitoneal fibrosis in patients receiving timolol maleate and in patients receiving other beta-adrenergic blocking agents. A causal relationship between this condition and therapy with beta-adrenergic blocking agents has not been established.

Hydrochlorothiazide _ Body as a Whole: weakness; Digestive: anorexia, gastric irritation, vomiting, cramping, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialadenitis; Nervous System/Psychiatric: vertigo, pares-thesias, restlessness; Hematologic: leukopenia, agranu-locytosis, thrombocytopenia, aplastic anemia, hemolytic anemia; Cardiovascular: hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs); Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions; Metabolic: hyperglycemia, glycosuria, hyperuri-cemia, electrolyte imbalance (see PRECAUTIONS); Musculoskeletal: muscle spasm; Renal: renal failure, renal dysfunction, interstitial nephritis, (see WARNINGS); Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia; Special Senses: transient blurred vision, xanthopsia.

Potential Adverse Effects: In addition, a variety of adverse effects not observed in clinical trials with timolol maleate, but reported with other beta-adrenergic blocking agents, should be considered potential adverse effects of timolol maleate: Nervous System: reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performances on neuropsychometrics; Cardiovascular: intensification of AV block (see CONTRAINDICATIONS); Digestive: mesenteric arterial thrombosis, ischemic colitis; Hematologic: agranulocytosis, thrombocytopenic purpura; Allergic: erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Miscellaneous: Peyronie†s disease.

There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis, and sclerosing serositis attributed to the beta-adrenergic receptor blocking agent, practolol. This syndrome has not been reported with TIMOLIDE (timolol maleate-hydrochlorothiazide) or BLOCADREN* (timolol maleate).

Clinical Laboratory Test Findings: Clinically important changes in standard laboratory parameters were rarely associated with the administration of TIMOLIDE (timolol maleate-hydrochlorothiazide) . The changes in laboratory parameters were not progressive and usually were not associated with clinical manifestations. The most common changes were increases in serum triglycerides and uric acid and decreases in serum potassium and chloride. Decreases in HDL cholesterol have been reported.

Read the Timolide (timolol maleate-hydrochlorothiazide) Side Effects Center for a complete guide to possible side effects


TIMOLIDE (timolol maleate-hydrochlorothiazide) may potentiate the action of other antihyper-tensive agents used concomitantly. Close observation of the patient is recommended when TIMOLIDE (timolol maleate-hydrochlorothiazide) is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.

Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by non-steroidal anti-inflammatory drugs has been reported. In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when TIMOLIDE (timolol maleate-hydrochlorothiazide) and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired therapeutic effect has been obtained.

Literature reports suggest that oral calcium antagonists may be used in combination with beta-adrenergic blocking agents when heart function is normal, but should be avoided in patients with impaired cardiac function. Hypotension, AV conduction disturbances, and left ventricular failure have been reported in some patients receiving beta-adrenergic blocking agents when an oral calcium antagonist was added to the treatment regimen. Hypotension was more likely to occur if the calcium antagonist were a dihydropyridine derivative, e.g. nifedipine, while left ventricular failure and AV conduction disturbances were more likely to occur with either verapamil or diltiazem.

Intravenous calcium antagonists should be used with caution in patients receiving beta-adrenergic blocking agents.

The concomitant use of beta-adrenergic blocking agents with digitalis and either diltiazem or verapamil may have additive effects in prolonging AV conduction time.

Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with quinidine and timolol, possibly because quinidine inhibits the metabolism of timolol via the P-450 enzyme, CYP2D6.

Beta adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the beta adrenergic blocking agent should be withdrawn several days before the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta adrenergic blocking agents should be delayed for several days after clonidine administration has stopped.

Risk from Anaphylactic Reaction: While taking beta blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.

In patients receiving thiazides, sensitivity reactions may occur with or without a history of allergy or bronchial asthma. The possible exacerbation or activation of systemic lupus erythematosus has been reported. The antihypertensive effects of thiazides may be enhanced in the post-sympathectomy patient.

Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude the therapeutic effectiveness of norepinephrine. Thiazides may increase the responsiveness to tubocurarine.

Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Read circulars for lithium preparations before use of such preparations with TIMOLIDE (timolol maleate-hydrochlorothiazide) .

Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochloro-thiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 1/28/2005

Side Effects

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