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Metatensin 2 Side Effects

Generic Name: reserpine / trichlormethiazide

Note: This page contains information about the side effects of reserpine / trichlormethiazide. Some of the dosage forms included on this document may not apply to the brand name Metatensin 2.

Applies to reserpine / trichlormethiazide: oral tablet

Metabolic

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.

Rare cases of hypercalcemia and milk-alkali syndrome (hypercalcemia, metabolic alkalosis, and renal insufficiency) have been associated with the use of a related drug, chlorothiazide.[Ref]

Metabolic changes associated with trichlormethiazide, as with other thiazide diuretics, are relatively common, especially when daily doses greater than 4 mg are used. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50% of patients, and may increase the risk of cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypophosphatemia, hypercalcemia, hyperglycemia, hypercholesterolemia, and hyperuricemia are also relatively common. The electrolyte and intravascular fluid shifts that may occur during trichlormethiazide diuresis can provoke hepatic encephalopathy in patients with hepatic cirrhosis.[Ref]

Cardiovascular

A woman with paroxysmal atrial tachycardia developed sinus pauses during reserpine therapy which were reproducible by carotid massage, except when isoproterenol was given. Reserpine is known to increase vagal tone and to deplete cardiac catecholamines.

One patient, in a series of 231, with emergent hypertension, stroke, and thyrotoxic crisis developed profound hypotension after 1 mg of reserpine (IM) was given. Her blood pressure dropped from 180/100 to an unmeasurable level. The patient recovered after isoproterenol therapy.[Ref]

Cardiovascular side effects associated with reserpine include hypotension in 8% and bradycardia (and rare cases of syncope with bradycardia) in 3% of patients. The risk of orthostatic hypotension is increased with the addition of trichlormethiazide due to the risk of intravascular volume depletion. A rare case of paroxysmal atrial tachycardia with block associated with reserpine in a patient who was not taking a digitalis preparation and rare cases of cerebrovascular accident associated with thiazide-induced diuresis have been reported.[Ref]

Respiratory

Rare reports of reserpine-induced bronchospasm are believed to be due to inactivation of beta-adrenergic receptors, which can result in a marked potentiation of the bronchoconstrictive effect of histamine.[Ref]

Respiratory system side effects are probably due to the reserpine component of this combination drug. Nasal congestion has occurred in 8% of patients on the combination product, and rare cases of bronchospasm have been associated with the use of reserpine alone.[Ref]

Nervous system

Nervous system side effects associated with reserpine include sedation, lethargy (different from the psychiatric syndrome of depression), drowsiness, weakness, vertigo, insomnia, or headache in approximately 1% to 5% of patients. While reserpine is used to treat tardive dyskinesia, extrapyramidal movements may worsen upon withdrawal of therapy. A case of CNS hypertension, believed to be due to cerebral edema, has been associated with reserpine. General fatigue, visual disturbances and insomnia have been rarely associated with trichlormethiazide.[Ref]

Increased parkinsonian movements upon reserpine withdrawal (as with neuroleptics) may be due to supersensitivity to dopamine as a result of increased dopamine receptors that developed during reserpine therapy.[Ref]

Hypersensitivity

Hypersensitivity reactions to thiazides usually involve the skin (cutaneous vasculitis, urticaria, rash, purpura), but may involve the gastrointestinal system (nausea, vomiting, or diarrhea), the genitourinary system (interstitial nephritis), and the respiratory system (acute noncardiogenic pulmonary edema, pneumonitis). Thiazide diuretics may induce phototoxic dermatitis.[Ref]

Thiazides may induce allergic reactions in patients who are allergic to sulfonamides.[Ref]

Psychiatric

The depressive syndrome usually consists of melancholy, loss of self confidence, early morning awakening, loss of libido, and reduced appetite.

A case of reserpine withdrawal psychosis has been reported. This uncommon condition may be due to dopamine receptor supersensitivity, which develops during reserpine therapy.[Ref]

Psychiatric problems related to reserpine therapy can be serious. Depression occurs in 2% to 28% of patients, is more likely when daily doses exceed 0.5 mg, and can present at any time during therapy. Suicidal ideation has been reported. Reserpine-induced depression is quickly reversible if therapy is withdrawn as soon as the syndrome is recognized, but can persist for several months after drug discontinuation if the syndrome fully develops. Reserpine withdrawal psychosis has been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects due to unopposed parasympathetic activity produced by catecholamine depletion may lead to increased gastrointestinal motility and secretory activity. Because of this, new diarrhea or worsening of existing diarrhea or increased salivation has been reported in 2% to 5% of patients. Vomiting, constipation or abdominal pain has been reported in approximately 5% of patients who are taking trichlormethiazide, and increased appetite, abdominal pain, or vomiting has been reported in less than 5% of patients who are taking reserpine. Rare cases of acute cholecystitis or pancreatitis have been associated with trichlormethiazide.[Ref]

A retrospective case-controlled drug surveillance study has revealed the relative risk of acute cholecystitis associated with the use of a thiazide diuretic is 2.0. The suspected explanation for this association is the potentially deleterious effect thiazides have on the serum lipid profile. Trichlormethiazide-induced hypercholesterolemia or hypertriglyceridemia may enhance the formation of some types of gallstones.[Ref]

Dermatologic

Dermatologic reactions may indicate hypersensitivity to trichlormethiazide. Erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis (including toxic epidermal necrolysis), and alopecia have been reported in rare cases.[Ref]

Genitourinary

Genitourinary complaints are limited to impotence in approximately 5% of male patients who are taking either reserpine or trichlormethiazide.[Ref]

Endocrine

Endocrinologic changes associated with thiazide diuretics include decreased glucose tolerance and a potentially deleterious effect on the lipid profile. This may be important in some patients with or who are at risk for diabetes or coronary artery disease. Abnormalities due to reserpine-induced hyperprolactinemia include gynecomastia in men and breast engorgement or pseudolactation in women.[Ref]

Renal

Renal side effects including new or worsened renal insufficiency associated with trichlormethiazide therapy is a probable sign of intravascular volume depletion, and serves as a signal to reduce or withhold therapy. Rare cases of allergic interstitial nephritis have been associated with the use of some thiazide diuretics.[Ref]

Hematologic

Hematologic side effects are rare. Rare cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with the use of thiazide diuretics.[Ref]

Musculoskeletal

Musculoskeletal cramping or spasms have occasionally been associated with trichlormethiazide-induced diuresis.[Ref]

Immunologic

Immunologic side effects are rare. A single case of angioimmunoblastic lymphadenopathy has been associated with reserpine. In one study of 231 patients, only one case of a lupus-like syndrome was observed. The patient previously received hydralazine.[Ref]

A 79-year-old woman with hypertension, taking reserpine, potassium, hydrochlorothiazide and ibuprofen, developed fatigue, anorexia, fever, night sweats, and weight loss. Associated laboratory finding showed anemia, lymphocytosis, thrombocytopenia, IgA kappa paraproteinemia, a positive ANA, and a positive Coombs' test. Bone marrow biopsy, lymphangiography, and lymph node biopsy showed bone marrow lymphocytosis, enlarged foamy abdominal lymph nodes with irregular filling, and angioimmunoblastic lymphadenopathy, respectively. Within four days after discontinuation of reserpine (her other medications were continued), the paraprotein level normalized and the platelet count rose. After an additional nine months of prednisone therapy, all signs and symptoms resolved.[Ref]

Oncologic

Oncologic concerns were raised after a large drug surveillance center in Boston reported an association between reserpine, a stimulator of prolactin, and breast cancer in 1974. This association was partially, but not completely, confirmed in two similar centers in Europe. A critical review of these studies elucidated several design flaws. Subsequent, controlled studies failed to show an association between reserpine and an increased incidence of breast carcinoma.[Ref]

References

1. "Product Information. Metatensin (reserpine-trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.

2. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28

3. Coe FL, Kavalach AG "Hypercalciuria and hyperuricosuria in patients with calcium nephrolithiasis." N Engl J Med 291 (1974): 1344-50

4. el-Meheiry MM, Nabih AE, Soliman MD "A clinical study of a new diuretic, Trichlormethiazide." J Trop Med Hyg 69 (1966): 209-14

5. Takeda R, Ueno T, Tsutchiya M, Kawasaki S, Masuya H "Sinus arrest following diuretic therapy in a patient with myxedema and hypertension." Cardiology 60 (1975): 185-91

6. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9

7. Murayama M, Yasuda K, Minamori Y, Mercado-Asis LB, Yamakita N, Miura K "Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation." J Clin Endocrinol Metab 75 (1992): 935-42

8. Combs RM "Unusual response to reserpine in paroxysmal atrial tachycardia with block unassociated with digitalis." South Med J 60 (1967): 839-42

9. Pfeifer HJ, Greenblatt DK, Koch-Wester J "Clinical toxicity of reserpine in hospitalized patients: a report from the Boston Collaborative Drug Surveillance Program." Am J Med Sci 271 (1976): 269-76

10. Stokkeland OM, Sangvik K, Ditlefsen EM "A comparative study of metoprolol and trichlormethiazide in hypertension." Curr Ther Res Clin Exp 18 (1975): 755-68

11. Applegate WB, Carper ER, Kahn SE, Westbrook L, Linton M, Baker MG, Runyan JW, Jr "Comparison of the use of reserpine versus alpha-methyldopa for second step treatment of hypertension in the elderly." J Am Geriatr Soc 33 (1985): 109-15

12. Berlant JL "Neuroleptics and reserpine in refractory psychoses." J Clin Psychopharmacol 6 (1986): 180-4

13. Widmer RB "Reserpine: the maligned antihypertensive drug." J Fam Pract 20 (1985): 81-3

14. Kirschenbaum HL, Rosenberg JM "What to look out for with guanethidine and reserpine." RN 47 (1984): 31-3

15. Sharon E, Paolino JS, Kaplan D "Hematemesis after reserpine for Raynaud's phenomenon." Ann Intern Med 77 (1972): 479-80

16. Luxenberg J, Feigenbaum LZ "The use of reserpine for elderly hypertensive patients." J Am Geriatr Soc 31 (1983): 556-9

17. Diamond L "Drug-induced bronchospasm." J Clin Pharmacol J New Drugs 10 (1970): 215-6

18. Atuk NO, Owen JA, Jr "Bronchospasm after reserpine." N Engl J Med 281 (1969): 908-9

19. Freis ED "Reserpine in hypertension: present status." Am Fam Physician 11 (1975): 120-2

20. Gibb WE, Malpas JS, Turner P, White RJ "Comparison of bethanidine, alpha-methyldopa, and reserpine in essential hypertension." Lancet 2 (1970): 275-7

21. Segal MS "Bronchospasm after reserpine." N Engl J Med 281 (1969): 1426-7

22. Peters HA "Questioning reserpine's adverse effect on tardive dyskinesia." Am J Psychiatry 140 (1983): 1106

23. Goodwin FK, Bunney WE, Jr "Depressions following reserpine: a reevaluation." Semin Psychiatry 3 (1971): 435-48

24. Bacher NM, Lewis HA "Reserpine and tardive dyskinesia." Am J Psychiatry 141 (1984): 719

25. Donatelli A, Geisen L, Feuer E "Case report of adverse effect of reserpine on tardive dyskinesia." Am J Psychiatry 140 (1983): 239-40

26. Reus VI "Behavioral side effects of medical drugs." Prim Care 6 (1979): 283-94

27. Ross RT "Drug-induced parkinsonism and other movement disorders." Can J Neurol Sci 17 (1990): 155-62

28. Dilsaver SC, Greden JF "Possible cholinergic mechanism in reserpine and tardive dyskinesia." Am J Psychiatry 141 (1984): 151-2

29. Samuels AH, Taylor AJ "Reserpine withdrawal psychosis." Aust N Z J Psychiatry 23 (1989): 129-30

30. Lewis WH "Iatrogenic psychotic depressive reaction in hypertensive patients." Am J Psychiatry 127 (1971): 1416-7

31. Fleishman M "Letter: Reserpine, ECT, and depression." Am J Psychiatry 132 (1975): 1088

32. Ambrosino SV "Depressive reactions associated with reserpine." N Y State J Med 74 (1974): 860-4

33. Kent TA, Wilber RD "Reserpine withdrawal psychosis: the possible role of denervation supersensitivity of receptors." J Nerv Ment Dis 170 (1982): 502-4

34. Blumenthal M, Davis R, Doe RP "Carcinoid syndrome following reserpine therapy in thyrotoxicosis." Arch Intern Med 116 (1965): 819-23

35. Dillon PT, Babe J, Meloni CR, Canary JJ "Reserpine in thyrotoxic crisis." N Engl J Med 283 (1970): 1020-3

36. Jinnouchi T, Mimura G, Sadanaga T, Ono K, Sakamoto Y "Proceedings: Study on the effect of long-term administration (one year) of trichlormethiazide upon glucose metabolism of SHR." Jpn Heart J 17 (1976): 412-3

37. Entrican JH, Denburg JA, Gauldie J, Kelton JG "Angioimmunoblastic lymphadenopathy associated with reserpine." Lancet 2 (1984): 820-1

38. Newball HH, Byar DP "Does reserpine increase prolactin and exacerbate cancer of prostate? Case control study." Urology 2 (1973): 525-9

Not all side effects for Metatensin 2 may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

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