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Guanethidine Side Effects

For the Consumer

Applies to guanethidine: oral tablet

In addition to its needed effects, some unwanted effects may be caused by guanethidine. In the event that any of these side effects do occur, they may require medical attention.

Severity: Moderate

If any of the following side effects occur while taking guanethidine, check with your doctor or nurse as soon as possible:

More common:
  • Swelling of feet or lower legs
Less common or rare:
  • Chest pain
  • shortness of breath

Minor Side Effects

Some of the side effects that can occur with guanethidine may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:
  • Diarrhea or increase in bowel movements
  • dizziness, lightheadedness, or fainting, especially when getting up from a lying or sitting position
  • sexual problems in males
  • slow heartbeat
  • stuffy nose
  • unusual tiredness or weakness
Less common or rare:
  • Blurred vision
  • drooping eyelids
  • dryness of mouth
  • headache
  • loss of hair on scalp
  • muscle pain or tremors
  • nausea or vomiting
  • nighttime urination
  • skin rash

For Healthcare Professionals

Applies to guanethidine: oral tablet


The risk of orthostatic hypotension, sometimes followed by syncope, is greatest within the first 10 minutes after dosing, early in the morning, and in hypovolemic patients. It is accentuated by alcohol, hot weather, or exercise--all of which are associated with peripheral vasodilation. The manufacturer recommends that guanethidine be gradually withdrawn over at least two weeks prior to administration of general anesthetics to avoid cardiovascular collapse during induction.[Ref]

Cardiovascular side effects can result from excessive sympathetic blockade or a relative increase in parasympathetic tone. Orthostatic hypotension is reported in approximately 15% of patients, some of whom experience syncope.

Unopposed or excessive parasympathetic tone can cause excessive bradycardia in rare cases. This may cause serious problems in patients with underlying sinus node dysfunction.

Guanethidine can cause generalized edema in 10% to 15% of patients. Some patients with preexisting congestive heart failure do not tolerate this, and require concomitant diuretic therapy.[Ref]


Gastrointestinal side effects are also related to increased parasympathetic tone. Diarrhea is reported in 11% of patients, some of whom discontinued therapy because of it. Dry mouth or parotid tenderness are reported in approximately 5% of patients.[Ref]


There is evidence that guanethidine may interfere with ejaculation by inhibiting contraction of the seminal vesicle, ampula and ductus deferens.[Ref]

Large studies report sexual impotence as a relatively uncommon genitourinary complaint, occurring in only approximately 2% of male patients. Smaller studies, where specific questions were asked of male patients reveal an incidence of impotence as high as 60%. Delayed or retrograde ejaculation and decreased sperm counts are reported. Impotence appears to be reversible upon discontinuation of therapy or reduction in dosage.[Ref]


A relatively common respiratory system complaint, nasal stuffiness in up to 30% of patients, is related to increased parasympathetic tone. Rare reports of dyspnea or exertion unaccompanied by other signs or symptoms of congestive heart failure are associated with guanethidine.[Ref]


In one study, 58% of patients with or without preexisting elevated BUN developed an increase in the BUN during guanethidine therapy. The study did not, however, quantify the rise in BUN, attempt to make an association with the degree of blood pressure control, or attempt to measure other parameters of renal function.[Ref]

Nervous system

Because guanethidine does not affect the central nervous system, neurologic side effects are notably either absent or infrequent. Insomnia and weakness are occasionally reported more often with guanethidine than with placebo.[Ref]


Hypersensitivity reactions are not associated with guanethidine.[Ref]


1. Walter IE, Nies AS "Safety of single large oral doses of guanethidine." Clin Pharmacol Ther 21 (1977): 706-8

2. Sharpe E, Milaszkiewicz R, Carli F "A case of prolonged hypotension following intravenous guanethidine block." Anaesthesia 42 (1987): 1081-4

3. "Product Information. Ismelin (guanethidine)." Ciba Pharmaceuticals, Summit, NJ.

4. Kalmanovitch DV, Hardwick PB "Hypotension after guanethidine block." Anaesthesia 43 (1988): 256

5. Hansson L, Pascual A, Julius S "Comparison of guanadrel and guanethidine." Clin Pharmacol Ther 14 (1973): 204-8

6. Weil JV, Chidsey CA "Plasma volume expansion resulting from interference with adrenergic function in normal man." Circulation 37 (1968): 54-61

7. Grunstein JA "The problem of postural hypotension." Gerontol Clin (Basel) 16 (1974): 171-4

8. Adi FC, Eze CJ, Anwunah A "Comparison of debrisoquine and guanethidine in treatment of hypertension." Br Med J Mar (1975): 482-5

9. Jadad AR, Carroll D, Glynn CJ, Mcquay HJ "Intravenous regional sympathetic blockade for pain relief in reflex sympathetic dystrophy: a systematic review and a randomized, double-blind crossover study." J Pain Symptom Manage 10 (1995): 13-20

10. Dollery CT, Emslie-Smith D, Milne MD "Clinical and pharmacological studies with guanethidine in the treatment of hypertension." Lancet Aug (1960): 381-7

11. Leishman AW, Sandler G "Guanethidine and hypertension after five years." Angiology 18 (1967): 705-16

12. Kaplan R, Claudio M, Kepes E, Gu XF "Intravenous guanethidine in patients with reflex sympathetic dystrophy." Acta Anaesthesiol Scand 40 (1996): 1216-22

13. Tarpley EL "Controlled trial of guanethidine and methyldopa in moderate hypertension." Curr Ther Res Clin Exp 16 (1974): 1187-96

14. Rowe J, Bassan MM "Symptomatic sick sinus syndrome due to guanethidine." Hypertension 1 (1979): 543-6

15. Goldberg LI, Zimmerman AM "Guanethidine and methyldopa as therapeutic agents in hypertension: a comparative review." Postgrad Med June (1963): 548-54

16. Scheinman MM, Strauss HC, Evans GT, et al "Adverse effects of sympatholytic agents in patients with hypertension and sinus node dysfunction." Am J Med 64 (1978): 1013-20

17. Malinow SH "Comparison of guanadrel and guanethidine efficacy and side effects." Clin Ther 5 (1983): 284-9

18. Ramirez EA, Elson L, Freis ED, et al "Multiclinic controlled trial of bethanidine and guanethidine in severe hypertension." Circulation 55 (1977): 519-25

19. Bulpitt CJ, Dollery CT "Side effects of hypotensive agents evaluated by a self-administered questionnaire." Br Med J 3 (1973): 485-90

20. Woosley RL, Nies AS "Guanethidine." N Engl J Med 295 (1976): 1053-8

21. Bauer GE, Hull RD, Stokes GS, Raftos J "The reversibility of side effects of guanethidine therapy." Med J Aust May (1973): 930-3

22. Kedia K, Markland C "The effect of pharmacological agents on ejaculation." J Urol 114 (1975): 569-73

Not all side effects for guanethidine 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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