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Salutensin Side Effects

Generic name: hydroflumethiazide / reserpine

Note: This document contains side effect information about hydroflumethiazide / reserpine. Some dosage forms listed on this page may not apply to the brand name Salutensin.

Applies to hydroflumethiazide / reserpine: oral tablet.


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, milk-alkali syndrome (hypercalcemia, metabolic alkalosis, and renal insufficiency) have been associated with thiazide diuretics.[Ref]

Metabolic changes associated with hydroflumethiazide (HFT), as with other thiazide diuretics, are relatively common, especially when daily doses greater than 100 mg are used. The electrolyte and intravascular fluid shifts that may occur during HFT diuresis can provoke hepatic encephalopathy in patients with hepatic cirrhosis. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50%, and may predispose patients to cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypophosphatemia, hypercalcemia, hyperglycemia, hypercholesterolemia, and hyperuricemia are also relatively common.[Ref]


Cardiovascular side effects associated with reserpine include hypotension in 8% and bradycardia (and rare cases of syncope with bradycardia) in 3% of patients. Orthostatic hypotension may be more likely with the addition of HFT due to intravascular volume depletion. Rare cases of cerebrovascular accident associated with thiazide-induced diuresis have been reported.[Ref]

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 receiving 1 mg of reserpine IM. Her blood pressure dropped from 180/100 to an unmeasurable level. The patient recovered after isoproterenol 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]

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]


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. Chlorothiazide-induced hypercholesterolemia or hypertriglyceridemia may enhance the formation of some types of gallstones.[Ref]

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 are reported in 2% to 5% of patients. Other GI problems that occur in approximately 5% of patients include anorexia, gastric irritation, nausea, vomiting, constipation, or abdominal pain in approximately 5% of patients. Thiazide diuretics have been associated with acute cholecystitis, intrahepatic cholestatic jaundice and rare cases of pancreatitis.[Ref]


Respiratory system side effects may be due to reserpine. Nasal congestion is reported in 8% of patients. Rare cases of bronchospasm have been associated with reserpine.[Ref]

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]

Nervous system

Nervous system side effects that are commonly 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. Mild or transient dizziness, fatigue, and headache have been associated with HFT. 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.[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]


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 values. A control group was not reported.[Ref]

Endocrinologic changes associated with HFT, as with other thiazides, 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. Reserpine-induced hyperprolactinemia can result in gynecomastia in men and breast engorgement or pseudolactation in women.[Ref]


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]


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


Renal side effects including new or worsened renal insufficiency 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 some thiazide diuretics.[Ref]


Genitourinary complaints are limited to impotence, reported in approximately 5% of male patients.[Ref]


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

A 40-year-old woman with valvular heart disease developed listlessness, fatigue, easy bruising, increased pallor and exercise intolerance over 4 years after starting HFT 100 mg twice a week. She was taking no other medications. Physical and laboratory examination revealed petechiae, ecchymoses, optic hemorrhages, fever, signs of congestive heart failure, and gross pancytopenia. Sternal marrow aspiration revealed hypoplasia, except for a slight increase in lymphocytes and plasma cells. Iron stores were abundant. The patient fully recovered over a 10-week period after steroids, transfusions, phytohemagglutinin, fluoxymesterone (to suppress menstruation and to induce erythropoiesis), and discontinuation of HFT.[Ref]


Musculoskeletal cramping or spasms are occasionally reported during HFT-induced diuresis.[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 findings 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]

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 had previously received hydralazine.[Ref]


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]


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

3. Raskind M (1974) "Psychosis, polydipsia, and water intoxication. Report of a fatal case." Arch Gen Psychiatry, 30, p. 112-4

4. Jamil MA (1971) "A comparative study of spironolactone and hydroflumethiazide alone and together in the treatment of hypertension." Guys Hosp Rep, 120, p. 207-19

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

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

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

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

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

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

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

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

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

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

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

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

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27. Reus VI (1979) "Behavioral side effects of medical drugs." Prim Care, 6, p. 283-94

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31. Segal MS (1969) "Bronchospasm after reserpine." N Engl J Med, 281, p. 1426-7

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

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

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

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42. Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM (1981) "Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion." Arch Int Pharmacodyn Ther, 253, p. 154-63

43. Williamson JM, Neilson FJ, Gibbs WN (1966) "Hypoplastic anaemia and hydroflumethiazide." Scott Med J, 11, p. 19-20

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

45. Mack TM, Henderson BE, Gerkins VR, et al. (1975) "Reserpine and breast cancer in a retirement community." N Engl J Med, 292, p. 1366-71

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47. Curb JD, Hardy RJ, Labarthe DR, Borhani NO, Taylor JO (1982) "Reserpine and breast cancer in the Hypertension Detection and Follow- Up Program." Hypertension, 4, p. 307-11

48. Labarthe DR, O'Fallon WM (1980) "Reserpine and breast cancer. A community-based longitudinal study of 2,000 hypertensive women." JAMA, 243, p. 2304-10

49. Jick H (1975) "Editorial: Reserpine and breast cancer: a perspective." JAMA, 233, p. 896-7

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

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.