Timolide Side Effects

Generic Name: hydrochlorothiazide / timolol

Note: This page contains side effects data for the generic drug hydrochlorothiazide / timolol. It is possible that some of the dosage forms included below may not apply to the brand name Timolide.

It is possible that some side effects of Timolide may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to hydrochlorothiazide / timolol: oral tablet

As well as its needed effects, hydrochlorothiazide / timolol may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking hydrochlorothiazide / timolol, check with your doctor immediately:

Less common
  • Blurred vision
  • chest pain or discomfort
  • confusion
  • cough
  • difficult or labored breathing
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
  • lightheadedness, dizziness, or fainting
  • noisy breathing
  • shortness of breath
  • slow or irregular heartbeat
  • sweating
  • tightness in chest
  • unusual tiredness or weakness
  • wheezing
Rare
  • Bloody or cloudy urine
  • dilated neck veins
  • extreme fatigue
  • fast heartbeat
  • irregular breathing
  • pain in lower back or side
  • small clicking, bubbling, or rattling sounds in the lung when listening with a stethoscope
  • swelling of face, fingers, feet, or lower legs
  • weight gain
Incidence not determined
  • Ankle, knee, or great toe joint pain
  • fixed position of eye
  • headache
  • inability to speak
  • joint stiffness or swelling
  • muscle cramps
  • seizures
  • severe numbness, especially on one side of the face or body
  • severe or sudden headache
  • slurred speech
  • temporary blindness
  • weakness in arm and/or leg on one side of the body, sudden and severe

Some hydrochlorothiazide / timolol side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

Less common
  • Lack or loss of strength
Rare
  • Acid or sour stomach
  • belching
  • darkening of skin color
  • decreased interest in sexual intercourse
  • diarrhea
  • difficulty having a bowel movement (stool)
  • difficulty in moving
  • having a hard time focusing or doing everyday activities
  • heartburn
  • inability to have or keep an erection
  • indigestion
  • joint pain
  • loss in sexual ability, desire, drive, or performance
  • muscle aching, pains, or stiffness
  • nausea
  • nervousness
  • rash
  • sleepiness or unusual drowsiness
  • sleeplessness
  • stomach discomfort, upset, or pain
  • swollen joints
  • trouble sleeping
  • unable to sleep
Incidence not determined
  • Earache

For Healthcare Professionals

Applies to hydrochlorothiazide / timolol: oral tablet

General

Timolol-hydrochlorothiazide (HCTZ) is generally well tolerated. Most side effects are mild and transient.[Ref]

Cardiovascular

Cardiovascular side effects have included sinus bradycardia and hypotension. Sinus bradycardia is reported in 1.2% of the patients, but is reported in up to 9% of patients who are taking timolol alone. Hypotension is reported in 1.6% of patients, and can result in syncope, particularly in the elderly. Atrioventricular conduction disturbances or exacerbation of congestive heart failure are reported in less than 1% of patients. Rarely, HCTZ-induced hypokalemia can predispose some patients to significant cardiac arrhythmias, including ventricular ectopy and complete AV heart block.[Ref]

Metabolic

Metabolic side effects associated with HCTZ are more common when daily doses exceed 50 mg. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50% of patients, and may predispose patients to cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, and elevated serum uric acid levels are also relatively common. Timolol-HCTZ may increase serum cholesterol and decrease HDL lipoprotein cholesterol.[Ref]

Since HCTZ may increase total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, VLDL lipoprotein cholesterol levels by 50%, and may reduce insulin secretion, timolol-HCTZ should be used with caution in diabetic patients and in those with hypercholesterolemia. Timolol, like some other beta-blockers, may also have an unfavorable effect on the lipid profile.

Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.[Ref]

Respiratory

Alternative therapy should be considered in patients with reactive airways disease. Case reports of fatal respiratory arrests have been reported in patients with asthma who were given timolol, even after topical ophthalmic administration.

A case of refractory rhinitis has been reported, thought to be due to timolol-induced vasomotor rhinitis.[Ref]

Respiratory problems associated with timolol-HCTZ, as with other drugs that contain beta-antagonists, include bronchial constriction in susceptible patients. Dyspnea is reported in 1% to 6% of patients. There are approximately 30 case reports of acute noncardiogenic pulmonary edema associated with HCTZ. The mechanism is not known, but may be due to hypersensitivity to the drug.[Ref]

Hypersensitivity

A 68-year-old man with a history of myocardial infarction (MI) developed dyspnea, chest tightness, a low grade fever, dizziness, sweating, and vomiting associated with cyanosis, a mild leukocytosis, radiographic evidence of pulmonary edema, clinical evidence of hypovolemia, and respiratory acidosis. MI and infection were ruled out; the patient recovered after restoration of his intravascular volume with saline and albumin. The only precipitating factor per history was the ingestion of HCTZ, which the patient had taken without incident for two years. Rechallenge resulted in recurrent acute pulmonary edema. Other signs of hypersensitivity, such as rash and eosinophilia, were absent.[Ref]

Hypersensitivity reactions occur in less than 1% of patients. They may present as nausea, vomiting, diarrhea, or rash. Case reports of acute pulmonary edema, interstitial cystitis, interstitial nephritis, and anaphylaxis have been reported.[Ref]

Dermatologic

A 67-year-old white woman with hypothyroidism, hypercalcemia, depression, and hypertension developed facial erythema, headaches, tremors, confusion, and personality changes associated with a new positive ANA and anti-nRNP, and skin biopsy consistent with lupus erythematosus while taking HCTZ, levothyroxine, and amitriptyline. The eruption resolved upon discontinuation of HCTZ, but she later developed a higher ANA titer associated with symptomatic diffuse interstitial pulmonary infiltrates. She was successfully treated with corticosteroids.[Ref]

Dermatologic reactions are usually due to the HCTZ component. Thiazides may induce phototoxic dermatitis, erythema annular centrifugum, acute eczematous dermatitis, and morbilliform or leukocytoclastic vasculitis. In addition, a rare, distinct entity with clinical and laboratory features indistinguishable from those of subacute cutaneous lupus erythematosus has been associated with HCTZ. Rare cases of generalized psoriasis and hyperpigmented nailbeds have been associated with timolol.[Ref]

Nervous system

Nervous system side effects include fatigue in 2% to 6%, headache in 4%, and dizziness in 6% of patients. Rare cases of worsened myasthenia gravis, visual hallucinations, insomnia, and depression have been associated with timolol, and rare cases of cerebrovascular insufficiency have been associated with HCTZ-induced plasma volume contraction.[Ref]

A case of amaurosis fugax has been associated with timolol, but the patient had underlying cerebrovascular disease, autonomic dysfunction, and an arrhythmia.[Ref]

Renal

Renal side effects including new or worsened renal insufficiency may occur due to HCTZ-induced intravascular volume depletion. Rare cases of interstitial nephritis have been associated with HCTZ.[Ref]

Although HCTZ has been used to treat nephrogenic diabetes insipidus, a case report in which the drug was believed to have caused this condition has been reported.[Ref]

Endocrine

Endocrinologic side effects associated with timolol, as with other non-selective beta-blockers, include masking the signs and symptoms and blunting the normal physiologic response to hypoglycemia. Both timolol and HCTZ may cause an increase in serum triglycerides, LDL, and VLDL cholesterol, and a decrease in HDL cholesterol. Thiazide diuretics may induce glucose intolerance. Some of these side effects may be important in patients with or who are at risk for diabetes or coronary artery disease.[Ref]

A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed an increased mean fasting blood glucose level after treatment. Withdrawal of thiazide therapy for 7 months in 10 of the patients resulted in mean reductions of 10% in fasting blood glucose and 25% in the 2-hour glucose tolerance test value. A control group was not reported.[Ref]

Gastrointestinal

Gastrointestinal complaints of general abdominal pain, nausea, constipation, or diarrhea have been reported in less than 1% of patients. There have been rare reports of pancreatitis and acute cholecystitis associated with HCTZ.[Ref]

Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in an increased risk of cholesterol gallstone formation. Reports of bowel strictures associated with thiazide ingestion have been reported in the 1960's, although these patients were on a combination HCTZ-potassium product.[Ref]

Psychiatric

Psychiatric side effects, such as confusion, depression (including acute suicidal ideation), vivid and frightening dreams, or visual hallucinations have been associated with timolol.[Ref]

Musculoskeletal

Musculoskeletal pains are reported in less than 1% of patients.[Ref]

Genitourinary

Genitourinary complaints of impotence and decreased libido are rare.[Ref]

Immunologic

Immunologic reactions are extremely rare. A single case of reversible systemic lupus erythematosus has been associated with ophthalmic timolol solution and rare cases of allergic vasculitis have been associated with HCTZ.[Ref]

An 86-year-old man with glaucoma who was taking timolol 0.5% eyedrops developed fever, malaise, pleurisy, and recurrent sterile pleural effusions associated with antinuclear and histone antibodies. The syndrome resolved completely after discontinuation of timolol.

There are rare case reports of HCTZ-induced immune hemolytic anemia. The following illustrates a fatal case:

A 53-year-old man with hypertension developed nausea, vomiting, diarrhea, and progressive anorexia and weakness associated with scleral icterus, anemia with spherocytosis, dark red urine with proteinuria, bilirubinuria, hemoglobinuria, and elevated serum lactate dehydrogenase levels 18 months after beginning HCTZ and methyldopa. Haptoglobin was less than 50 mg/dl. Direct and indirect Coombs tests were positive. The patient died suddenly; autopsy revealed no obvious cause of death, left ventricular hypertrophy, and mild coronary atherosclerosis.[Ref]

Hematologic

Hematologic side effects have not been reported during therapy with the combination product. Cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with HCTZ.[Ref]

References

1. Hoss DM, Nierenberg DW "Severe shaking chills and fever following hydrochlorothiazide administration." Am J Med 85 (1988): 747

2. Clark BG, Vestal RE "Adverse drug reactions in the elderly: case studies." Geriatrics 39 (1984): 53-66

3. Mashford ML, Coventry D, Hecker R, et al. "Adverse Drug Reactions Advisory Committee: ADRAC report for 1980." Med J Aust 1 (1982): 416-9

4. Papademetriou V, Fletcher R, Khatri IM, Freis ED "Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias." Am J Cardiol 52 (1983): 1017-22

5. Dunn FG, Frohlich ED "Pharmacokinetics, mechanisms of action, indications, and adverse effects of timolol maleate, a nonselective beta-adrenoreceptor blocking agent." Pharmacotherapy 1 (1981): 188-200

6. Altus P "Timolol-induced congestive heart failure." South Med J 74 (1981): 88

7. Treseder AS, Thomas TP "Sinus arrest due to timolol eye drops." Br J Clin Pract 40 (1986): 256-8

8. Hollifield JW, Slaton PE "Thiazide diuretics, hypokalemia and cardiac arrhythmias." Acta Med Scand Suppl 647 (1981): 67-73

9. Yates D "Syncope and visual hallucinations, apparently from timolol." JAMA 244 (1980): 768-9

10. "Product Information. Timolide (timolol-hydrochlorothiazide)." Merck & Co, Inc, West Point, PA.

11. Fraunfelder FT, Meyer SM "Sexual dysfunction secondary to topical ophthalmic timolol." JAMA 253 (1985): 3092-3

12. Holland OB, Kuhnert L, Pollard J, Padia M, Anderson RJ, Blomqvist G "Ventricular ectopic activity with diuretic therapy." Am J Hypertens 1 (1988): 380-5

13. Ragnarsson J, Hardarson T, Snorrason SP "Ventricular dysrhythmias in middle-aged hypertensive men treated either with a diuretic agent or a beta-blocker." Acta Med Scand 221 (1987): 143-8

14. Mouallem M, Friedman E, Shemesh Y, Mayan H, Pauzner R, Farfel Z "Cardiac conduction defects associated with hyponatremia." Clin Cardiol 14 (1991): 165-8

15. Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,

16. Bain PG, Egner W, Walker PR "Thiazide-induced dilutional hyponatraemia masquerading as subarachnoid haemorrhage ." Lancet 2 (1986): 634

17. Murphy MB, Kohner E, Lewis PJ, Schumer B, Dollery CT "Glucose intolerance in hypertensive patients treated with diuretics: a fourteen-year follow-up." Lancet 2 (1982): 1293-5

18. Fager G, Berglund G, Bondjers G, Elmfeldt D, Lager I, Olofsson SO, Smith U, Wiklund O "Effects of anti-hypertensive therapy on serum lipoproteins. Treatment with metoprolol, propranolol and hydrochlorothiazide." Artery 11 (1983): 283-96

19. Pinnock CA "Hyponatraemia associated with hydrochlorothiazide treatment ." Br Med J 1 (1978): 48

20. Klimiuk PS, Davies M, Adams PH "Primary hyperparathyroidism and thiazide diuretics." Postgrad Med J 57 (1981): 80-3

21. Safran AB, Simona F, Sansonetti A, Pometta D, James R "Effects of ocular carteolol and timolol on plasma high-density lipoprotein cholesterol level." Am J Ophthalmol 117 (1994): 683

22. Seelig CB "Magnesium deficiency in two hypertensive patient groups." South Med J 83 (1990): 739-42

23. Byatt CM, Millard PH, Levin GE "Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions." J R Soc Med 83 (1990): 704-8

24. Benfield GF, Haffner C, Harris P, Stableforth DE "Dilutional hyponatraemia masquerading as subarachnoid haemorrhage in patient on hydrochlorothiazide/amiloride/timolol combined drug ." Lancet 2 (1986): 341

25. Polanska AI, Baron DN "Hyponatraemia associated with hydrochlorothiazide treatment ." Br Med J 1 (1978): 175-6

26. Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860

27. Morris R, Bulteau P "Respiratory arrest after beta-blocker in an asthmatic patient." Med J Aust 2 (1980): 576

28. Botet C, Grau J, Benito P, Coll J, Vivancos J "Timolol ophthalmic solution and respiratory arrest." Ann Intern Med 105 (1986): 306-7

29. Laursen SO, Bjerrum P "Timolol eyedrop-induced severe bronchospasm." Acta Med Scand 211 (1982): 505-6

30. Swenson ER "Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist." Arch Intern Med 146 (1986): 1220-1

31. Biron P, Dessureault J, Napke E "Acute allergic interstitial pneumonitis induced by hydrochlorothiazide [published erratum appears in Can Med Assoc J 1991 Sep 1;145(5):391]." Can Med Assoc J 145 (1991): 28-34

32. Frishman WH "Atenolol and timolol, two new systemic beta-adrenoceptor antagonists." N Engl J Med 306 (1982): 1456-62

33. Odeh M, Oliven A, Bassan H "Timolol eyedrop-induced fatal bronchospasm in an asthmatic patient." J Fam Pract 32 (1991): 97-8

34. Prince DS, Carliner NH "Respiratory arrest following first dose of timolol ophthalmic solution." Chest 84 (1983): 640-1

35. Grace AA, Morgan AD, Strickland NH "Hydrochlorothiazide causing unexplained pulmonary oedema." Br J Clin Pract 43 (1989): 79-81

36. Levay ID "Hydrochlorothiazide-induced pulmonary edema." Drug Intell Clin Pharm 18 (1984): 238-9

37. Hoegholm A, Rasmussen SW, Kristensen KS "Pulmonary oedema with shock induced by hydrochlorothiazide: a rare side effect mimicking myocardial infarction." Br Heart J 63 (1990): 186

38. Alted E, Navarro M, Cantalapiedra JA, Alvarez JA, Blasco MA, Nunez A "Non-cardiogenic pulmonary edema after oral ingestion of hydrochlorothiazide ." Intensive Care Med 13 (1987): 364-5

39. Kaufman HS "Timolol-induced vasomotor rhinitis: a new latrogenic syndrome." Arch Ophthalmol 104 (1986): 967, 970

40. Charan NB, Lakshminarayan S "Pulmonary effects of topical timolol." Arch Intern Med 140 (1980): 843-4

41. Hayes LP, Stewart CJ, Kim I, Mohr JA "Timolol side effects and inadvertant overdosing." J Am Geriatr Soc 37 (1989): 261-2

42. Klein MD "Noncardiogenic pulmonary edema following hydrochlorothiazide ingestion." Ann Emerg Med 16 (1987): 901-3

43. Dunn TL, Gerber MJ, Shen AS, Fernandez E, Iseman MD, Cherniak RM "The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects." Am Rev Respir Dis 133 (1986): 264-8

44. Dorn MR, Walker BK "Noncardiogenic pulmonary edema associated with hydrochlorothiazide therapy." Chest 79 (1981): 482-3

45. Fernandez-Vozmediano JM, Blasi NA, Romero-Cabrera MA, Carracosa-Cerquero A "Allergic contact dermatitis to timolol." Contact Dermatitis 14 (1986): 252

46. Diffey BL, Langtry J "Phototoxic potential of thiazide diuretics in normal subjects." Arch Dermatol 125 (1989): 1355-8

47. Parodi A, Romagnoli M, Rebora A "Subacute cutaneous lupus erythematosus-like eruption caused by hydrochlorothiazide." Photodermatol 6 (1989): 100-2

48. Feiler-Ofry V, Godel V, Lazar M "Nail pigmentation following timolol maleate therapy." Ophthalmologica 182 (1981): 153-6

49. Goodrich AL, Kohn SR "Hydrochlorothiazide-induced lupus erythematosus: a new variant?" J Am Acad Dermatol 28 (1993): 1001-2

50. Kubota K, Koyama E, Yasuda K "Skin irritation induced by topically applied timolol." Br J Clin Pharmacol 31 (1991): 471-5

51. Puig L, Goni FJ, Roque AM, Bordas FD, Morgas JM "Psoriasis induced by ophthalmic timolol preparations." Am J Ophthalmol 108 (1989): 455-6

52. Baldone JA, Hankin JS, Zimmerman TJ "Allergic conjunctivitis associated with timolol therapy in an adult." Ann Ophthalmol 14 (1982): 364-5

53. Coppeto JR "Timolol-associated myasthenia gravis." Am J Ophthalmol 98 (1984): 244-5

54. Shore JH, Fraunfelder FT, Meyer SM "Psychiatric side effects from topical ocular timolol, a beta-adrenergic blocker." J Clin Psychopharmacol 7 (1987): 264-7

55. Berstein LP, Henkind P "Additional information on adverse reactions to timolol." Am J Ophthalmol 92 (1981): 295-6

56. Verkijk A "Worsening of myasthenia gravis with timolol maleate eyedrops." Ann Neurol 17 (1985): 211-2

57. Coppeto JR "Transient ischemic attacks and amaurosis fugax from timolol." Ann Ophthalmol 17 (1985): 64-5

58. Perell H, Campbell DG, Vela A, Henderson B "Choroidal detachment induced by a systemic beta-blocker." Ophthalmology 95 (1988): 410-1

59. Balizet L "Recurrent parathyroid adenoma. Association with prolonged thiazide administration." JAMA 225 (1973): 1238-9

60. Velde TM, Kaiser FE "Ophthalmic timolol treatment causing altered hypoglycemic response in a diabetic patient." Arch Intern Med 143 (1983): 1627

61. Leren P, Foss PO, Nordvik B, Fossbakk B "The effect of enalapril and timolol on blood lipids." Acta Med Scand 223 (1988): 321-6

62. Wagner W, Longerbeam JK, Smith LL, Feikes HL "Drug-induced ulcers of the small bowel causing intestinal obstruction or perforation." Am Surg 33 (1967): 7-11

63. Dietz MW "Iatrogenic jejunal ulcer." Am J Roentgenol Radium Ther Nucl Med 99 (1967): 136-8

64. White HD, Antman EM, Glynn MA, et al "Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery." Circulation 70 (1984): 479-84

65. Reinus FZ, Weinberger HA, Fischer WW "Medication-induced ulceration of the small bowel." Am J Surg 112 (1966): 97-101

66. Nolan BT "Acute suicidal depression associated with use of timolol." JAMA 247 (1982): 1567

67. Lynch MG, Whitson JT, Brown RH, Nguyean H, Drake MM "Topical beta-blocker therapy and central nervous system side effects: a preliminary study comparing betaxolol and timolol." Arch Ophthalmol 106 (1988): 908-11

68. Sharir M, Nardin GF, Zimmerman TJ "Timolol maleate associated with phalangeal swelling." Arch Ophthalmol 109 (1991): 1650

69. Lustgarten JS "Topical timolol-induced arthropathy." Am J Ophthalmol 105 (1988): 687-8

70. Shirey RS, Bartholomew J, Bell W, Pollack B, Kickler TS, Ness PM "Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia." Transfusion 28 (1988): 70-2

71. Zamber RW, Starkebaum G, Rubin RL, Martens HF, Wener MH "Drug induced systemic lupus erythematosus due to ophthalmic timolol." J Rheumatol 19 (1992): 977-9

72. Beck ML, Cline JF, Hardman JT, Racela LS, Davis JW "Fatal intravascular immune hemolysis induced by hydrochlorothiazide." Am J Clin Pathol 81 (1984): 791-4

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