Diamox Sequels Side Effects

Generic Name: acetazolamide

Note: This page contains information about the side effects of acetazolamide. Some of the dosage forms included on this document may not apply to the brand name Diamox Sequels.

Not all side effects for Diamox Sequels may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to acetazolamide: oral capsules, oral tablets, parenteral powder for injection

Side effects include:

Paresthesias, hearing dysfunction or tinnitus, anorexia, altered taste, nausea, vomiting, diarrhea, polyuria, drowsiness, confusion.

For Healthcare Professionals

Applies to acetazolamide: compounding powder, injectable powder for injection, oral capsule extended release, oral tablet

Metabolic

Because it inhibits carbonic anhydrase in the renal proximal tubule, acetazolamide (the active ingredient contained in Diamox Sequels) can cause a bicarbonate diuresis and metabolic acidosis. The following case is illustrative:

A 61-year-old man with a history of glaucoma, diabetic ketoacidosis, myocardial infarction, and renal insufficiency developed mental lethargy and disorientation while taking acetazolamide 250 mg four times a day. He was also taking furosemide, potassium, metoclopramide, and eye drops (timolol, atropine, and pilocarpine). The most remarkable associated findings included an anion gap of 15, serum glucose of 97 mg/dl, and arterial blood gas values of pH = 7.23, p02 = 68 mm Hg, bicarbonate 6 mEq/L, and paC02 = 14 mm Hg. Serum ketones were absent; other pertinent laboratory values, including serum calcium, spinal tap findings, ECG, head CT and cultures were negative. An EEG revealed findings consistent with a metabolic encephalopathy. The patient recovered after acetazolamide was withheld and a total of 140 mEq of sodium bicarbonate was infused over a 12-day period. A follow-up analysis revealed type IV renal tubular acidosis when acetazolamide, potassium and bicarbonate were withheld.[Ref]

Metabolic side effects have included metabolic acidosis and electrolyte imbalance (hypokalemia). Rare cases of severe metabolic acidosis, hypocalcemia, or hypophosphatemia have been reported. Many patients who have developed metabolic acidosis have either had renal insufficiency, diabetes mellitus, or both. Metabolic derangements may be more likely and more severe in patients with renal dysfunction.[Ref]

Ocular

Ocular side effects have included rare reports of local paresthesias, transient myopia, and choroidal detachment.[Ref]

Nervous system

Nervous system side effects have included weakness, lethargy, drowsiness, and paresthesias. A "tingling" feeling in the extremities has been reported in up to 20% of patients. Rare nervous system side effects have included tinnitus or hearing dysfunction and alteration of taste (dysgeusia). Profound muscle weakness has been associated with the use of acetazolamide (the active ingredient contained in Diamox Sequels) in patients with periodic paralysis.[Ref]

Dysgeusia following ingestion of some foods, particularly carbonated beverages, has been associated with use of acetazolamide.

While acetazolamide has been used to successfully alleviate myotonia in patients with hypokalemic or hyperkalemic periodic paralysis, it has also been associated with reversible quadriparesis in rare cases.

A small series of patients who developed spastic craniofacial syndromes associated with some diuretics, including acetazolamide, has been reported. The serum calcium levels were not reported in this series.[Ref]

Psychiatric

Acetazolamide increases the urinary excretion of bicarbonate. The resulting increase in the pH of the urine decreases the excretion of titratable acid and of ammonia. Urinary alkalinization in effect diverts ammonia from the renal tubules into the systemic circulation. This can be detrimental to patients with liver disease.

A single case of major depression associated with the use of acetazolamide (the active ingredient contained in Diamox Sequels) eye drops has been reported. The patient's depression was refractory to drug therapy, and resolved upon discontinuation of acetazolamide. A rechallenge was not attempted.[Ref]

Psychiatric side effects have included rare reports of delirium associated with acetazolamide-induced metabolic acidosis. A single case of major depression has been associated with the use of this drug.[Ref]

Renal

Renal side effects have included rare reports of new or worsened renal insufficiency, nephrolithiasis, or nephrocalcinosis. The drug can cause alkalinization of the urine, decreased citrate excretion, and mild hypercalciuria. As a non-bacteriostatic sulfonamide, the drug can cause sulfonamide crystalluria. Rare cases of acute renal failure without evidence of obstruction have been associated with the use of acetazolamide (the active ingredient contained in Diamox Sequels) [Ref]

A 33-year-old woman with hypertension, pseudotumor cerebri, status post-renal transplant developed progressive renal dysfunction within 3 days of starting acetazolamide 750 mg/day. Her antihypertensive and immunosuppressive medications remained unchanged, and there was no evidence of dehydration, hypotension, infection, obstruction, or transplant rejection. The possible catabolic influence of high-dose corticosteroids was excluded by a normal BUN to creatinine ratio and by the fact that her renal function began to improve during high-dose corticosteroid therapy. Arterial blood gases showed a mild metabolic acidosis. The patient's renal function returned to baseline within four days after stopping acetazolamide.[Ref]

Hypersensitivity

Hypersensitivity reactions have included rare reports of toxic epidermal necrolysis, Stevens-Johnson syndrome, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Two cases of fatal anaphylaxis have been associated with the use of this drug.[Ref]

A 66-year-old woman with glaucoma developed laryngeal edema and severe respiratory distress after the first dose of acetazolamide 250 mg. The patient died despite intensive care. She had previously taken topical timolol and dipivefrin without adverse consequences. There was no history of allergy or hypersensitivity.

A 54-year-old man with glaucoma developed progressive weakness, anorexia, rash, abdominal pain, nausea, vomiting, diarrhea, and delirium within days after beginning acetazolamide 500 mg/day. Physical examination was remarkable for a diffuse erythematous rash, signs of peripheral circulatory failure, jaundice, a flapping tremor, hiccups, and extreme tenderness in the right hypochondrium. Laboratory examination was mostly remarkable for a serum bicarbonate of 7 mEq/L and an anion gap of 23. The patient developed acute renal failure and died. Autopsy revealed marked hepatic cholestasis with widespread fatty infiltration, compatible with drug intoxication, and an anterior mediastinal Hodgkin's lymphoma.[Ref]

Hematologic

Hematologic side effects have included rare reports of myelosuppression. Thrombocytopenia, leukopenia, and even pancytopenia and aplastic anemia have been reported.[Ref]

Idiosyncratic aplastic anemia has been associated with the use of sulfonamides. Acetazolamide is a sulfonamide derivative.

A retrospective Swedish study revealed 11 cases of acetazolamide-associated aplastic anemia during a 17-year period. Given the rate of acetazolamide use during that period, the reported incidence was one in 17,800 patient-years, and the calculated relative risk was 13.3.[Ref]

Genitourinary

Genitourinary side effects have included rare reports of decreased libido or impotence.[Ref]

Musculoskeletal

Musculoskeletal side effects have included a single case of gouty arthritis, which was believed to be related to hyperuricemia secondary to acetazolamide-induced decreased renal excretion of uric acid.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, and diarrhea. A single case each of erosive gastritis and hypersensitivity hepatitis has been associated with the use of acetazolamide (the active ingredient contained in Diamox Sequels) [Ref]

A 65-year-old man with glaucoma developed anorexia, dyspnea on exertion, upper abdominal pain, and weight loss within two months after starting acetazolamide. Physical and biochemical examinations were basically unremarkable except for a gastroscopy which showed small superficial ulcerations in the antrum and pylorus. After switching from acetazolamide to timolol for intraocular pressure reduction, the patient's symptoms resolved. A repeat gastroscopy was normal.[Ref]

Dermatologic

Dermatologic side effects have included a single case of exacerbation of rosacea after oral administration. Intravenous administration has been complicated by extravasation and rare cases of skin ulceration.[Ref]

Drugs like acetazolamide which act as peripheral vasodilators (e.g., nitrates and calcium channel blockers) have been known to exacerbate rosacea.[Ref]

Other

Other side effects have included confusion and stupor.[Ref]

General

General side effects have included fever.[Ref]

References

1. Reid W, Harrower AD "Acetazolamide and symptomatic metabolic acidosis in mild renal failure ." Br Med J (Clin Res Ed) 284 (1982): 1114

2. Berthelsen P "Cardiovascular performance and oxyhemoglobin dissociation after acetazolamide in metabolic alkalosis." Intensive Care Med 8 (1982): 269-74

3. Watson WA, Garrelts JC, Zinn PD, Garriott JC, McLemore TL, Clementi WA "Chronic acetazolamide intoxication." J Toxicol Clin Toxicol 22 (1984-85): 549-63

4. Gabay EL "Metabolic acidosis from acetazolamide therapy ." Arch Ophthalmol 101 (1983): 303-4

5. Reiss WG, Oles KS "Acetazolamide in the treatment of seizures." Ann Pharmacother 30 (1996): 514-9

6. Patton RD, Berkowitz R, Buchwald RP, Stein E "Hypothermia and profound acidosis due to benign prostatic hyperplasia." J Urol 105 (1971): 547-8

7. Maisey DN, Brown RD "Acetazolamide and symptomatic metabolic acidosis in mild renal failure." Br Med J (Clin Res Ed) 283 (1981): 1527-8

8. Mallette LE "Acetazolamide-accelerated anticonvulsant osteomalacia." Arch Intern Med 137 (1977): 1013-7

9. De Marchi S, Cecchin E "Severe metabolic acidosis and disturbances of calcium metabolism induced by acetazolamide in patients on haemodialysis." Clin Sci 78 (1990): 295-302

10. Cowan RA, Hartnell GG, Lowdell CP, Baird IM, Leak AM "Metabolic acidosis induced by carbonic anhydrase inhibitors and salicylates in patients with normal renal function." Br Med J (Clin Res Ed) 289 (1984): 347-8

11. Maren TH "Acetazolamide and advanced liver disease ." Am J Ophthalmol 102 (1986): 672-3

12. Siklos P, Henderson RG "Severe acidosis from acetazolamide in a diabetic patient." Curr Med Res Opin 6 (1979): 284-6

13. Heller I, Halevy J, Cohen S, Theodor E "Significant metabolic acidosis induced by acetazolamide: not a rare complication." Arch Intern Med 145 (1985): 1815-7

14. Goodfield M, Davis J, Jeffcoate W "Acetazolamide and symptomatic metabolic acidosis in mild renal failure ." Br Med J (Clin Res Ed) 284 (1982): 422

15. Fan JT, Johnson DH, Burk RR "Transient myopia, angle-closure glaucoma, and choroidal detachment after oral acetazolamide." Am J Ophthalmol 115 (1993): 813-4

16. "Product Information. Diamox (acetazolamide)." Lederle Laboratories, Wayne, NJ.

17. Miller LG, Miller SM "Altered taste secondary to acetazolamide therapy." J Fam Pract 31 (1990): 199-200

18. Meyer BH "The use of low-dose acetazolamide to prevent mountain sickness." S Afr Med J 85 (1995): 792-3

19. Torres CF, Griggs RC, Moxley RT, Bender AN "Hypokalemic periodic paralysis exacerbated by acetazolamide." Neurology 31 (1981): 1423-8

20. Schwenk MH, Stpeter WL, Meese MG, Singhal PC "Acetazolamide toxicity and pharmacokinetics in patients receiving hemodialysis." Pharmacotherapy 15 (1995): 522-7

21. Kristinsson A "Fatal reaction to acetazolamide." Br J Ophthalmol 51 (1967): 348-9

22. Riggs JE, Griggs RC, Moxley RT "Acetazolamide-induced weakness in paramyotonia congenita." Ann Intern Med 86 (1977): 169-73

23. MartinezMir I, Badenes JN, Larrea VP "Taste disturbance with acetazolamide." Ann Pharmacother 31 (1997): 373

24. Perchuk E "Spastic craniofacial syndrome precipitated by diuretics." N Y State J Med 75 (1975): 91-3

25. Theeuwes F, Bayne W, McGuire J "Gastrointestinal therapeutic system for acetazolamide: efficacy and side effects." Arch Ophthalmol 96 (1978): 2219-21

26. Margo CE "Acetazolamide and advanced liver disease." Am J Ophthalmol 101 (1986): 611-2

27. Kurtz S, Ashkenazi I, Melamed S "Major depressive episode secondary to antiglaucoma drugs ." Am J Psychiatry 150 (1993): 524-5

28. Rowe TO "Acetazolamide delirium ." Am J Psychiatry 134 (1977): 587-8

29. Shields MB, Simmons RJ "Urinary calculus during methazolamide therapy." Am J Ophthalmol 81 (1976): 622-4

30. Orchard RT, Taylor DJ, Parkins RA "Sulphonamide crystalluria with acetazolamide." Br Med J 3 (1972): 646

31. Hannedouche T, Lazaro M, Delgado AG, Boitard C, Lacour B, Grunfeld JP "Feedback-mediated reduction in glomerular filtration during acetazolamide infusion in insulin-dependent diabetic patients." Clin Sci 81 (1991): 457-64

32. Parikh JR, Nolan RL, Bannerjee A, Gault MH "Acetazolamide-associated nephrocalcinosis in a transplant kidney." Transplantation 59 (1995): 1742-3

33. West AE "Hematuria in acetazolamide (diamox) therapy." Crit Care Med 10 (1982): 197

34. Tawil R, Moxley RT 3d, Griggs RC "Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders." Neurology 43 (1993): 1105-6

35. Parfitt AM "Acetazolamide and sodium bicarbonate induced nephrocalcinosis and nephrolithiasis: relationship to citrate and calcium excretion." Arch Intern Med 124 (1969): 736-40

36. Korzets A, Gafter U, Floru S, Chagnac A, Zevin D "Deteriorating renal function with acetazolamide in a renal transplant patient with pseudotumor cerebri." Am J Kidney Dis 21 (1993): 322-4

37. Peralta J, Abelairas J, Fernandez-Guardiola J "Anaphylactic shock and death after oral intake of acetazolamide ." Am J Ophthalmol 114 (1992): 367

38. Gangitano JL, Foster SH, Contro RM "Nonfatal methazolamide-induced aplastic anemia." Am J Ophthalmol 86 (1978): 138-9

39. Wisch N, Fischbein FI, Siegel R, Glass JL, Leopold I "Aplastic anemia resulting from the use of carbonic anhydrase inhibitors." Am J Ophthalmol 75 (1973): 130-2

40. Kodjikian L, Durand B, Burillon C, Rouberol F, Grange JD, Renaudier P "Acetazolamide-induced thrombocytopenia." Arch Ophthalmol 122 (2004): 1543-4

41. McWhae JA, Chang J, Lipton JH "Drug-induced fatal aplastic anemia following cataract surgery." Can J Ophthalmol 27 (1992): 313-5

42. Lubeck MJ "Aplastic anemia following acetazolamide therapy." Am J Ophthalmol 69 (1970): 684-5

43. Rentiers PK, Johnston AC, Buskard N "Severe aplastic anemia as a complication of acetazolamide therapy." Can J Ophthalmol 5 (1970): 337-42

44. Keisu M, Wiholm BE, Ost A, Mortimer O "Acetazolamide-associated aplastic anaemia." J Intern Med 228 (1990): 627-32

45. Englund GW "Fatal pancytopenia and acetazolamide therapy." JAMA 210 (1969): 2282

46. Epstein RJ, Allen RC, Lunde MW "Organic impotence associated with carbonic anhydrase inhibitor therapy for glaucoma." Ann Ophthalmol 19 (1987): 48-50

47. Ferry AP, Lichtig M "Gouty arthritis as a complication of acetazolamide (diamox) therapy for glaucoma." Can J Ophthalmol 4 (1969): 145-7

48. Herman J, Nassar F, Dalli N "Endoscopically proved erosive gastritis due to acetazolamide." Isr J Med Sci 16 (1980): 866-7

49. Shah P, O'Donnell B, Pochkhanawala F, Tan CY "Severe exacerbation of rosacea by oral acetazolamide." Br J Dermatol 129 (1993): 647-8

50. Callear A, Kirkby G "Extravasation of acetazolamide." Br J Ophthalmol 78 (1994): 731

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