Palliative Medicine Matters - Hospice Pharmacia

Palliative Medicine Matters
Vol. 2, No. 1 • SPRING 2008
Management of Excessive Sweating
By: Jennifer Johansen, PharmD, BCPS; Nimmy Matthews, PharmD(c); Ellie Vershvovsky
Why and how do people sweat?
Sweating, also known as diaphoresis, is the mechanism that the body uses to maintain normal physiologic temperature
– around 37°C. 1 Sweating occurs when the internal temperature goes above the accepted range; as the sweat evaporates, the
body cools and returns to normal temperature. 2 Although sweating is usually a normal response mechanism, some patients
suffer from excessive sweating in the absence of acute stimuli (e.g. rigorous exercise). Excessive sweating, in these cases, may
be the result of medications or diseases, such as cancer, or the cause may be unknown. 3
When does sweating become a problem?
Excessive sweating, also known as hyperhidrosis, affects an estimated 14 - 28% of cancer patients. 3-7 Hyperhidrosis can
present as either focal (confined to the forehead, feet, palms, or armpits) or generalized (sweating that occurs all over the
body not just limited to the focal areas). Sweating problems can occur throughout the day, but generally worsen at night,
contributing to sleep disturbances. Excessive sweating results in feelings of self-consciousness and may contribute to or
cause health problems, such as dehydration or salt imbalance. 2 Sweat on the skin’s surface also acts as a breeding ground for
bacteria, especially between skin folds, which may develop into skin infections. 8
What are potential causes of hyperhidrosis?
Likely causes of acute sweating include pain, anxiety, and conditions that cause patients distress, like asthma attacks.
These are normal responses and typically sweating will stop when the stimulus subsides. Patients suffering from
endocrine diseases/imbalances, such as hyperthyroidism, diabetes mellitus, menopause, and pheochromocytoma may
commonly experience sweating episodes. Sweating can be seen in patients with Parkinson’s disease, those with stroke
and heart/lung disorders, or in those with myeloproliferative or malignant disorders. Autoimmune diseases, such as
9, 10
rheumatoid arthritis and systemic lupus erythematosus (SLE), could also trigger excessive sweating.
Excessive sweating may also be a side effect or an adverse drug reaction to medication. Some medications (e.g. phenytoin,
sulfonamides, procainamide) can cause fever, which in turn, may result in excessive sweating as the body tries to cool
itself. 11 Other medications such as corticosteroids (e.g. prednisone), non-steroidal endocrine-metabolic agents (e.g.
megestrol, anastrozole, and tamoxifen), long-term use of analgesics (e.g. oxycodone, methadone and other opioids), and
others may cause sweating in absence of fever. 12
Two life-threatening, but rare, adverse drug reactions where one of the signs may be excessive sweating are Neuroleptic
Malignant Syndrome (NMS) and Serotonin Syndrome (SS). 13-16 These reactions present very similarly (sweating with or without
fever, motor abnormalities, mental status changes) but are due to distinctly different medications and have distinguishing
characteristics. Serotonin syndrome can be triggered by antidepressant medications (e.g., fluoxetine, venlafaxine, doxepin) used
in combination with each other, or with other serotonergic medications, such as meperidine, tramadol, dextromethorphan,
or “triptan” migraine medications (e.g., sumatriptan). While SS typically occurs within 24 to 48 hours of the addition of a
second serotonergic medication, it can also occur when a patient previously stabilized on two serotonergic agents has the dose
of either medication increased. Serotonin syndrome is usually self-limiting once the offending medication has been removed;
however, quick identification is key to preventing complications such as renal failure or seizures.
Palliative Medicine Matters is Hospice Pharmacia’s newsletter devoted to promoting evidence-based palliative care.

Unlike SS, NMS has a slower onset and progression, with symptoms usually developing during the first two weeks
of neuroleptic therapy (e.g. haloperidol, olanzapine, promethazine). Patients experiencing NMS develop progressive
bradykinesia, which results in a state of immobilization, akinesia and stupor accompanied by “cogwheel” rigidity, fever,
and autonomic instability. NMS is not a dose-dependent phenomenon, but higher doses do present a risk factor.
How is excessive sweating treated?
Unfortunately, excessive sweating can be difficult to diagnose and is often left untreated. 6 Non pharmacologic measures
listed below should be instituted when sweating is causing discomfort and the underlying cause cannot be determined or
reversed. 8
- Minimize clothing
- Frequent showering or wipe the patient down with a cool cloth
- Keep windows open and/or use a fan
- Increase fluid intake when appropriate
- Avoid alcohol and hot and/or spicy foods
Pharmacologic management of sweating:
There are no practice guidelines for the management of hyperhidrosis resulting from an underlying condition or medication.
When possible, treat the underlying cause of the sweating; if that is not successful or feasible, there are some medications
that may help. While iontophoresis has been reported in literature, its use in the hospice population may be limited.
Topical agents are generally used to treat localized sweating, whereas systemic agents are used to treat generalized sweating.
Evidence for systemic agents is anecdotal or weak at best. The choice of a pharmacological agent should be based upon
patient compliance and adverse effects. Although the use of several herbal agents have been reported in literature, lack of
standardization and regulation in the United States limits their use. 17
Topical pharmacologic options (in no particular order):
1. Aluminum chloride hexahydrate (ACH) 2%: 18
Topical agent that temporarily blocks sweat glands on the skin surface, thereby reducing the secretion of sweat and eventually
causing atrophy of the secretory cells. Because the eccrine glands are inactive at night, ACH should be applied nightly to
affected areas so the medication can penetrate the skin. Initially, ACH should be applied once daily for one week and then
weekly for maintenance. This therapy often causes skin irritation, especially in the axillary region. To minimize irritation,
any remaining medication can be washed off in the morning, and baking soda can neutralize the area. ACH is most useful
when rapid control of focal sweating is desired, but effects disappear within 48 hours of stopping treatment. Also, although
patients stop sweating in the area where ACH is applied, they may begin to sweat in other areas as the body compensates.
2. Botulinum Toxin (BoTox): 19-21
Poisonous substance released by the bacteria Clostridium botulinum. When injected intradermally, it blocks the release of
acetylcholine at nerve endings, subsequently preventing the production of sweat by the eccrine glands. BoTox is effective
for focal sweating and is FDA approved for axillary (armpit) hyperhidrosis. Its full effect may take several weeks, but effects
may last 3-7 months.
Systemic pharmacological options (in no particular order):
9, 10, 22-25
3. Anticholinergics
Produce a drying effect by inhibiting synaptic acetylcholine, which may help reduce the production and secretion of sweat.
The dose required to be effective frequently causes side effects, such as dry mouth, blurred vision, constipation or urinary
retention, which may place elderly patients at more risk than benefit. In a case report, scopolamine reduced sweating
associated with opioid use. Other anticholinergics, such as benztropine and oxybutynin have been effective for general
primary hyperhidrosis.
4. Gabapentin: 26-28
Anticonvulsant often used to treat neuropathic pain. Gabapentin was found in a small case series to be beneficial in
terminally ill cancer patients with severe diaphoresis and in patients whose sweating is caused by cancer-related menopause
To cite this article: Johansen JL, Matthew N, Vershovovsky E. Management of Excessive Sweating. Palliative Medicine Matters. Spring 2008. 2(1).

or castration. Gabapentin appears to be well tolerated.
29, 30
5. Thioridazine:
Neuroleptic agent with anticholinergic properties used in the treatment of sweating. Although neuroleptics can cause
NMS, full or partial response to this medication has been seen in cancer patients. It should be used cautiously in patients
with cardiac disorders, especially those with or at risk for hypotension or arrhythmias.
31, 32
6. SSRIs:
Fluoxetine and paroxetine are primarily used to treat depression but have been used to treat hot flashes associated
with cancer.
7. Clonidine and Methyldopa: 33-37
These antihypertensives work centrally by stimulating alpha 2
adrenergic autoreceptors, which play a role in the body’s
mechanisms for sweating. Clonidine may be useful in the treatment of hyperhidrosis due to tricyclic antidepressants
and in treating hot flashes associated with cancer or menopause. Methyldopa has been used to treat hot flashes in
menopausal women. Both agents may cause significant hypotension and side effects such as dry mouth, constipation,
drowsiness, and fatigue.
Summary:
• Sweating is the body’s natural reaction to increased internal temperature which may be caused by acute reversible
causes such as a fever, or due to chronic irreversible causes, like end-stage malignancies.
• Excessive sweating (hyperhidrosis) is commonly seen in hospice patients. In these patients, sweating is usually a
symptom of their disease or is caused by their medications (e.g., opioids, SSRIs).
• Treatment of hyperhidrosis should be targeted by reversing the underlying cause, if possible.
• While botulinum toxin is the only FDA approved therapy for diaphoresis, other medications, such as aluminum
chloride hexahydrate, gabapentin, and anticholinergics may be reasonable alternatives in the hospice patient with
hyperhidrosis depending on the location and severity of the condition.
Reference List:
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3. Quigley C, Baines M. Descriptive epidemiology of sweating in a hospice population. J Palliat Care. 1997;13(1):22-26.
4. Grond S, Zech D, Diefenbach C, Bischoff A. Prevalence and pattern of symptoms in patients with cancer pain: a prospective
evaluation of 1635 cancer patients referred to a pain clinic. J Pain Symptom Manage. 1994;9(6):372-382.
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8. Stolman LP. Treatment of hyperhidrosis. J Drugs Dermatol. 2003;2(5):521-527.
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10. Lipsky B, Hisrschmann JV. Drug Fever. J Am Med Assoc. 1981;245(8):851-854.
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Greenwood village (CO): Thomson MICROMEDEX; c1974-2007 [cited 2007 May 31].
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14. Carbone J. The neuroleptic malignant and serotonin syndromes. Emerg Med Clin North Am. 2000;18(2):317-325.
15. Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am. 1993;77(1):185-202.
16. DeSmet P. Drug therapy: Herbal remedies. N Eng J Med. 2002;347(25):2046-2056.
17. Goh C. Aluminum chloride hexahydrate versus palmar hyperhidrosis. Evaporimeter assessment. Int J Dermatol. 1990;29:368.
18. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel
group, double blind, placebo controlled. Br Med J. 2001;323(7313):596-.
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over 16 months. Arch Dermatol. 2003;139:731-736.
Reference List Continued
(references continued on next page)
Please send comments or ideas for clinical topics to qualityoutcomes@excelleRx.com.

SPRING 2008
Palliative Medicine Matters
Additional copies of this
newsletter can be
downloaded from the
Quality Outcomes section of
www.hospicepharmacia.com
Dear Clinician,
We have renamed our newsletter to Palliative Medicine Matters. This issue describes The
Management of Excessive Sweating.
This newsletter is devoted to sharing clinical information and promoting an evidence-based
approach to topics in palliative medicine and symptom management. It is a production of
the Quality Outcomes team at excelleRx. Our team is dedicated to building the evidence
base and improving outcomes related to chronic illness and palliative care. We welcome your
feedback and questions as well as your suggestions for future topics.
We hope you find this publication a valuable resource.
Sincerely,
The Quality Outcomes Team • qualityoutcomes@excelleRx.com
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23. Tupker RA, Harmsze AM, Deneer VM. Oxybutynin therapy for generalized hyperhidrosis. Arch Dermatol. 2006;142(8):1065-1066.
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