REVIEW C H R I S T O P H E R L. TISDEL, M D B R I A N G. D O N L E Y , M D J A M E S J. SFERRA, M D Department of Orthopaedic Surgery, Cleveland Clinic Department of Orthopaedic Surgery, Cleveland Clinic Department of Orthopaedic Surgery, Cleveland Clinic Diagnosing and treating plantar fasciitis: A conservative approach to plantar heel pain ABSTRACT Plantar fasciitis is the most common cause of pain at the weight-bearing surface of the heel, and may coexist w i t h other sources of heel pain. This has led to a confusing array of treatment strategies, including surgery. We offer a simple, effective diagnostic and treatment algorithm that emphasizes nonsurgical treatment options for this often frustrating condition. K E Y POINTS Plantar fasciitis, the most common cause of plantar heel pain, is an overuse injury causing inflammation at the attachment of the plantar fascia to the medial tubercle of the calcaneus. Physical examination of a patient w i t h plantar heel pain often reveals a tight Achilles tendon, as noted by limited ankle dorsiflexion w i t h the knee in extension. Swelling of the heel is not common and, when associated w i t h painful medial-lateral compression of the calcaneus, may suggest a stress fracture. Regular stretching of the Achilles tendon and plantar fascia is the critical part of any treatment program for plantar fasciitis. Stretching three to five times a day eventually rehabilitates the tight, chronically inflamed fascia. LTHOUGH CLINICIANS TRY many different approaches to relieve heel pain associated with plantar fasciitis, the most common cause of plantar heel pain in adults, we encourage a conservative treatment approach in these patients, one that emphasizes protection and rehabilitation of the affected tissue in the heel. Surgery is a treatment option in plantar fasciitis; however, it is usually not necessary because of the success of nonsurgical techniques. W e have found that offering a safe and effective treatment scheme to an informed patient commonly resolves this frustrating condition without surgery. • CAUSES OF HEEL PAIN Plantar heel pain has many potential causes, 1 - 5 including: • Plantar fasciitis • Calcaneal stress fracture • Fat pad atrophy • Compressive and metabolic neuropathy • Infection • Ischemia • Tumors. P l a n t a r fasciitis T h e most common cause of heel pain is plantar fasciitis, an overuse injury causing inflammation. It occurs at the attachment of the plantar fascia to the medial tubercle of the calcaneus ( F I G U R E 1 ) and has been associated with excessive walking or running, as well as with middle age, obesity, and biomechanical disorders such as pes cavus, pes planus, and tight CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 66 • NUMBER 4 Downloaded from www.ccjm.org on September 5, 2014. For personal use only. All other uses require permission. APRIL 1999 2 3 1 PLANTAR F A S C I I T I S T I S D E L AND C O L L E A G U E S Achilles tendon. Repeated stress to the plantar fascia origin leads to micro-tears and chronic inflammatory changes (necrosis, fibrosis, chondroid metaplasia).2'5 The normally resilient fascia becomes stiffened and prone to re-injury, thus setting up a vicious circle of persistent pain. Plantar fasciitis is usually an overuse injury Other causes of plantar heel pain N e r v e i n p i n g e m e n t . The nerve to the abductor digitorum quinti muscle, which courses just superior to the origin of the plantar fascia, may become impinged. This can lead to pain that is often mistaken for plantar fasciitis. However, complicating the differential diagnosis, nerve impingement can also coexist with plantar fasciitis.4-6 Fat pad atrophy. Atrophy of the plantar heel fat pad, secondary to aging or to overzealous corticosteroid use, can produce a more central heel pain, often a separate entity from plantar fasciitis. Bone spur. Many patients visit their physician complaining of pain caused by a "bone spur" (calcaneal osteophyte), and many physicians presume that bone spurs are the cause of plantar heel pain. However, this is misleading: 50% of patients with heel pain do not have a bone spur, and 15% of non-painful adult heels do have a spur. Although rarely the cause of plantar heel pain, a bone spur within the flexor digitorum brevis muscle dorsal to the plantar fascia ( F I G U R E 1) is present radiographically in about 5 0 % of patients with heel pain.2'5 Pathologic changes have been observed at the origin of the plantar fascia from surgical specimens, located just plantar to the region of spur formation.2-5 However, even if a bone spur is present, it should not influence the treatment protocol. • DIAGNOSIS D e t a i l e d history A detailed history will often provide enough information to make the diagnosis of plantar fasciitis, and physical examination will confirm it. A complete description of the pain is essential. Patients typically describe their plantar heel pain in the following ways: • Deep aching pain (like a "bruise") under the heel brought on by standing or 232 C L E V E L A N D C L I N I C J O U R N A L OF M E D I C I N E VOLUME 66 • NUMBER 4 APRIL walking and relieved with rest. • "Start-up pain," ie, pain exacerbation with initial weight-bearing in the morning or when rising from a chair, is typical of plantar fasciitis. Start-up pain is improved after a few minutes of walking, but pain will worsen again with prolonged standing. • Pain of gradual onset. Patients often describe a gradual onset of pain, present for weeks to months prior to seeking attention. • Acute trauma or swelling is not common; however, further questioning may indicate a change of activity level or a change of shoe wear preceding pain onset. Pain associated with significant swelling, occurring primarily at rest or without "start-up" qualities, is not suggestive of plantar fasciitis. A complete history may elicit conditions associated with heel pain, such as diabetes, inflammatory arthropathies, and spinal disorders.1-3-7 Examination of t h e f o o t a n d ankle: seeking sources of pain The physical examination in suspected plantar fasciitis begins with observing the exposed foot and ankle during gait and stance. Record any deviations from a normal foot type and gait. In the directed foot examination of patients with plantar heel pain, the clinician can elicit pain by palpating the origin of the plantar fascia ( F I G U R E 1 ) . Pain may be exacerbated by dorsiflexing the ankle and the metatarsal phalangeal joints, which stretches the plantar fascia. Pain may also be noted more medially, near the origin of the abductor hallucis muscle, and may extend distally along the plantar fascia. A tight Achilles tendon, as noted by limited ankle dorsiflexion with the knee in extension, is commonly seen with this condition. 1-3 Swelling is not common and, when associated with painful medial-lateral compression of the calcaneus, suggests a stress fracture. Pain posterior to the origin of the plantar fascia is more likely secondary to fat pad atrophy or periostitis. A complete foot and ankle examination that includes neurovascular assessment should rule out most other causes of heel pain. An exam of other organ systems (ie, eyes, mouth, spine, joints) is appropriate when other pain etiologies are suspected. 1999 Downloaded from www.ccjm.org on September 5, 2014. For personal use only. All other uses require permission. • Plantar fasciitis: A n a t o m y , diagnosis, t r e a t m e n t Calcaneal stress f r a c t u r e Calcaneal osteophyte ( b o n e spur) r heel fat pad atrophy Plantar fasciitis Pain f r o m p l a n t a r fasciitis Pain f r o m fat pad atrophy A N A T O M Y Heel p a i n has m a n y possible causes, i n c l u d i n g c a l c a n e a l b o n e spurs, stress f r a c t u r e s , a n d a t r o p h y o f t h e calc a n e a l f a t pad. H o w e v e r , t h e m o s t c o m m o n cause is p l a n t a r fasciitis, a c o m b i n a t i o n o f o v e r u s e i n j u r y a n d a n i n f l a m m a t o ry process, o c c u r r i n g a t t h e a t t a c h m e n t o f t h e p l a n t a r fascia t o t h e m e d i a l t u b e r c l e o f t h e calcaneus ( a r r o w ) . DIAGNOSIS P a l p a t i o n o f t h e o r i g i n o f t h e p l a n t a r fascia elicits t h e p a i n o f p l a n t a r fasciitis; d o r s i f l e x i o n o f t h e a n k l e a n d t h e m e t a t a r s a l p h a l a n g e a l j o i n t s m a y exacerb a t e t h e p a i n . Pain p o s t e r i o r t o t h e o r i g i n o f t h e p l a n t a r fascia is m o r e l i k e l y secondary t o fat pad a t r o p h y or periostitis. Silicone o r plastic heel p a d or cup adds comfort t o w a l k i n g a n d j o g g i n g shoes Night splint w o r n t o b e d stretches t h e p l a n t a r fascia K e e p leg straight, foot flat on the ground TREATMENT O p t i o n s f o r p l a n t a r fasciitis are p r i m a r i l y c o n s e r v a t i v e a n d i n c l u d e plastic heel pads o r cups, a s p l i n t t o b e w o r n a t n i g h t , a n d s t r e t c h i n g exercises t o be d o n e t h r e e t o f i v e t i m e s a day. FIGURE 1 233 C L E V E L A N D C L I N I C J O U R N A L OF M E D I C I N E VOLUME 66 • NUMBER 4 Downloaded from www.ccjm.org on September 5, 2014. For personal use only. All other uses require permission. APRIL 1999 PLANTAR F A S C I I T I S Multiple injections of corticosteroids may cause fat pad atrophy or plantar fascia rupture T I S D E L AND C O L L E A G U E S Diagnostic studies: W h e n is further investigation a p p r o p r i a t e ? Plantar fasciitis is a diagnosis made by the history and physical examination. When other sources of pain are possible, ancillary tests may be appropriate. Lateral and axial radiographs of the heel are typically normal but may be used to rule out fractures, rheumatologic conditions, or tumors.8 Bone scan. When patients present with atypical or chronic symptoms, a triple-phase bone scan may provide useful information. Plantar fasciitis is confirmed by uptake at the origin of the fascia. 1-3 Calcaneal stress fractures will reveal intense uptake throughout the bone. A negative scan may suggest neurogenic or other extraskeletal pain sources. Blood work may be helpful when considering inflammatory arthropathies or infection. A standard rheumatoid panel that includes a complete blood count with differential, erythrocyte sedimentation rate, antinuclear antibodies, and rheumatoid factor can supplement findings of the history and examination. Electromyelography and nerve conduction studies can provide objective information regarding nerve involvement when dysesthesias are prominent; however, these tests can be uncomfortable and are often negative until late nerve pathology develops.4 • TREATMENT OF PLANTAR FASCIITIS Treatment options for plantar fasciitis vary widely, but treatment should always begin with a combination of nonsurgical modalities. Treatment guidelines are available, based on recent studies that asked patients to rate various techniques.2,7,9,10 W e recommend the fol- lowing treatment scheme, which usually resolves pain in 2 to 6 months. 2 ' 7 - 10 Initial conservative strategies Inform the patient. Begin treatment by educating the patient as to the cause of plantar heel pain and how he or she can actively participate in its cure, such as performing specific exercises ( F I G U R E 1 ) . Supportive shoes. First, emphasize a change to more supportive shoes (eg, walking or jogging shoes) for routine activities. Patients can insert over-the-counter soft, pli234 C L E V E L A N D CLINIC J O U R N A L OF MEDICINE V O L U M E 6 6 • NUMBER 4 APRIL able plastic (Silastic) heel pads or protective heel cups into these shoes for more comfort ( F I G U R E 1 ) . Walking barefoot or in slippers should be avoided. Non-weight-bearing exercise. Suggest that patients change their activities to avoid aggravating factors until the pain resolves. Switching from weight-bearing activities (eg, walking, jogging) to non-weight-bearing aerobic exercise (eg, biking, swimming) can be helpful. Stretching. We believe stretching is the critical part of any treatment program for plantar fasciitis. Regularly stretching the Achilles tendon and plantar fascia eventually rehabilitates the tight, chronically inflamed fascia. Prescribe patients a simple stretching routine, which they should do three to five times a day (FIGURE 1 ) . 2 . 1 0 Be sure to warn patients that stretching may exacerbate symptoms for 1 to 3 weeks, but encourage them to continue until the pain resolves. Nonsteroidal anti-inflammatory drugs often help speed pain relief. The patient may need to take the medication for several weeks or months until pain resolves, so monitoring against side effects (eg, gastritis, peptic ulcers) is important. Nighttime splint. If morning start-up pain is significant or resistant to the above treatments, a splint can be worn to bed to maintain plantar fascia stretch ( F I G U R E 1 ) . W h a t t o do if initial t r e a t m e n t fails Corticosteroid injection. For patients slow to improve, a corticosteroid injection near the plantar fascia origin may provide adequate pain relief. However, multiple injections are discouraged as they may cause fat pad atrophy or plantar fascia rupture.11 In recalcitrant cases, patients may need to take time off work or use a walking cast for 4 to 6 weeks,10 or both. Custom orthotic. If the patient has coexisting biomechanical foot problems such as pes planus or cavus, a custom foot orthotic may be beneficial. We recommend a semirigid orthotic that supports the longitudinal arch, takes some of the weight-bearing load away from the plantar calcaneus, and absorbs weightbearing stresses. However, only very few patients with plantar fasciitis require custom orthotics. 10 1999 Downloaded from www.ccjm.org on September 5, 2014. For personal use only. All other uses require permission. Surgical options. Nonsurgical techniques are successful in over 9 0 % of our patients. If pain persists after 6 to 12 months of an exhaustive conservative program, then surgery may be recommended. W h e n indicated, a partial release of the medial plantar fascia, along with decompression of the nerve to the abductor digiti quinti may effect a cure. Advise the patient that a prolonged recovery after surgery may be expected, with cure rates in the 8 0 % to 9 0 % range 1-3,5 • REFERENCES 1. Bordelon RL. Heel pain. In: Mann RA, Coughlin MJ, editors. Surgery of the Foot and Ankle, 6th ed. St. Louis: Mosby-Year Book, Vol 2, 1993:837-857. 2. Gill LH. Plantar fasciitis: Diagnosis and conservative management. J A m Acad Orthopaed Surg 1997; 5:109-117. Schepsis A A , Leach RE, Gorzyca J. Plantar fasciitis. Etiology, treatment, surgical results and review of literature Clin Orthop 1991; 266:185-196. 3. 4. 5. Let us hear your opinions about the Cleveland Schon LC, Glennon TP, Baxter DE. Heel pain syndrome: Electrodiagnostic support for nerve entrapment. Foot A n k l e 1993; 14:129-135. Tountas A A , Fornasier VL. Operative treatment of subcalcaneal pain. Clin Orthop 1996; 332:170-178. 6. Baxter DE, Pfeffer GB. Treatment of chronic heel pain by surgical release of the first branch of the lateral plantar nerve. Clin Orthop 1992; 279:229-236. 7. Wolgin M, Cook C, Graham C, Mauldin D. Conservative treatment of plantar heel pain: Long term follow-up. Foot A n k l e Int 1994; 15:97-102. Amis J, Jennings L, Graham D, Graham CE. Painful heel syndrome: Radiographic and treatment assessment. Foot A n k l e 1988; 9:91-95. 8. 9. 10. 11. Tisdel CL, Harper MC. Chronic plantar heel pain: Treatment w i t h a short leg walking cast. Foot Ankle Int 1996; 17:41-42. Pfeffer G. AO FAS Heel Pain Study Group. Paper presented at: W i n t e r Meeting of the American Orthopaedic Foot and A n k l e Society; March 1997; San Francisco. Clinic Journal of Medicine. Do you like current articles and sections? What topics would you like to see covered and how can we make the Journal more useful to you? PHONE 216.444.2661 FAX 216.444.9385 E-MAIL [email protected] WWW http://www.ccf.org/ed/ccjrn/ccjhome.htm CLEVELAND CLINIC JOURNAL OF MEDICINE The Cleveland Clinic Foundation 9500 Euclid Avenue, EE37 Cleveland, Ohio 44195 Sellman JR. Plantar fascia rupture associated w i t h corticosteroid injection. Foot Ankle Int 1994; 15(7):376-381. ADDRESS: Christopher L Tisdel, MD, Department of Orthopaedic Surgery, A41, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. 235 CLEVELAND CLINIC JOURNAL OF MEDICINE V O L U M E 6 6 • NUMBER 4 Downloaded from www.ccjm.org on September 5, 2014. For personal use only. All other uses require permission. APRIL 1999 In hypertension or angina... Convenient once-daily dosing The usual starting dose is 5 mg in hypertension or angina — In hypertension, small, fragile, or elderly individuals or patients with hepatic insufficiency may be started on 2.5 m g once dally Titration can proceed to 10 mg — Most angina patients will require 10 m g Can be taken with or without food An excellent side-effect profile NORVASC 5 mg(%) (N=296) NORVASC 10 mg (%) PLACEBO (%) SIDE EFFECTS Edema 3.0 10.8 0.6 Dizziness 3.4 3.4 1.5 Flushing 1.4 2.6 0.0 Palpitation 1.4 4.5 0.6 DOSE-RELATED (N=268) (N=520) -c ?V V L. s V < Once-Daily 5-mg and 10-mg tablets NORVASC (amlodipine besylate) The #1 Branded Cardiovascular Agent Worldwide 1 References: 1. IMS Midas sales data, 1Q98; and IMS America prescription data, April 1998.2. Neaton JD, Grimm RH Jr. Prineas RJ, et al, for the Treatment of Mild Hypertension Study Research Group. Treatment of Mild Hypertension Study: final results. JAMA. 1993;270:713-724.3. Hayduk K, Sauerbrey-Wullkopf N, Leverkus F. Initial dose finding of amlodipine in patients with essential hypertension, Eur Heart J. 1994; 15(suppl): 194A. 4. Data on file. Pfizer Ine, New York, NY. Pharmaceutical A m e r i c a n Heart | Roundtabte Member» Association • Brief Summary NORVASC® (amlodipine besylate) Tablets For Oral Use CONTRAINDICATIONS: NORVASC is contraindicated in patients with known sensitivity to amlodipine. WARNINGS: Increased Angina and/or Myocardial Infarction: Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated. PRECAUTIONS: General: Since the vasodilation induced by NORVASC is gradual in onset, acute hypotension has rarely been reported after oral administration of NORVASC. Nonetheless, caution should be exercised when administering NORVASC as with any other peripheral vasodilalor particularly in patients with severe aortic stenosis. Use in Patients with Congestive Heart Failure: In general, calcium channel blockers should be used with caution in patients with heart failure. NORVASC (5-10 mg per day)has been studied in a placebo-controlled trial of 1153 patients with NYHA Class III or IV heart failure on stable doses oí ACE inhibitor, digoxin, and diuretics. Follow-up was at least 6 months, with a mean of about 14 months. There was no overall adverse effect on survival or cardiac morbidity (as defined by life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure). NORVASC has been compared to placebo in four 8-12 week studies of patients with NYHA Class ll/lll heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or LVEF. Beta-Blocker Withdrawal: NORVASC is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of the beta-blocker. Patients with Hepatic Failure: Since NORVASC is extensively metabolized by the liver and the plasma elimination halflife (t Jf) is 56 hours in patients with impaired hepatic function, caution should be exercised when administering NORVASC to patients with severe hepatic impairment. Drug Interactions: In vitro data in human plasma indica:e that NORVASC has no effect on the protein binding of drugs tested (digoxin, phenytoin, warfarin, and indomethacin).Special studies have indicated that the co-administration of NORVASC with digoxin did not change serum digoxin le/els or digoxin renal clearance in normal volunteers; that coadministration with cimetidine did not alter the pharmacckinetics of amlodipine; and that co-administration with warfarin did not change the warfarin prothrombin response time. In clinical trials, NORVASC has been safely adminis'ered with thiazide diuretics, beta-blockers, angiotensin converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal antiinflammatory drugs, antibiotics, and oral hypoglycemic crugs. Drug/Laboratory Test Interactions: None known. Carcinogenesis, Mutagenesis, Impairment of Fertility: Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide daily dosage levels of 0.5,1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest dose (for mice, similar to, ard for rats twice* the maximum recommended clinical dose of 10 mg on a mg/m 2 basis), was close to the maximum tolerated dose for mice but not for rats. Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels. There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females 14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human dose of 10 mg on a mg/m 2 basis). Pregnancy Category C: No evidence of teratogenicity o* other embryo/fetal toxicity was found when pregnant rats or rabbits were treated orally with up to 10 ma/kg amlodipine (respectively 8 times* and 23 times* the maximum recommended human dose of 10 mg on a m g / n r basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats administered 10 mg/kg amlodipine :or 14 days before mating and throughout mating and gestation. Amlodipine has been shown to prolong both tfe gestation period and the duration of labor in rats at this dose. There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers: It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while NORVASC is administered. Pediatric Use: Safety and effectiveness of NORVASC in children have not been established. ADVERSE REACTIONS: NORVASC has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with NORVASC was vell-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with NORVASC were of mild or moderate severity. In controlled clinical trials directly comparing NORVASC (N =1730) in doses up to 10 mg to placebo (N=1250), discontinuation of NORVASC due to adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most common side effects are headache and edema. The incidence (%) of side effects which occurred in a dose related manner are as follows: edema (1.8% at 2.5 mg, 3.0% at i.Omg, and 10.8% at 10.0 mg, compared with 0.6% placebo); dizziness (1.1% at 2.5 mg, 3.4% at 5.0 mg, and 3.4% at 10.0 mg, compared with 1.5% placebo); flushing (0.7% at 2.5 mg, 1.4% at 5.0 mg, and 2.6% at 10.0 mg, compared with 0.0% placebo); and palpitation (0.7% at 2.5 mg, 1.4% at 5.0 mg, and 4.5% at 10.0 mg, compared with 0.6% placebo). Other adverse experiences which were not clearly dose related but which were reported with an incidence greater than 1.0% in placebo-controlled clinical trials include thefollowing: headache (7.3%, compared with 7.8% placebo); fatigue (4.5%, compared with 2.8% placebo); nausea (2.9%, compared with 1.9% placebo); abdominal pain (1.6%, compared with 0.3% placebo); and somnolence (1.4%, compared with 0.6% placebo). For several adverse experiences that appear to be d'ug and dose related, there was a greater incidence in women than men associated with amlodipine treatment as follows: edema (5.6% in men, 14.6% in women, compared with a placebo incidence in men of 1.4% and 5.1% in women); fUshing (1.5% in men, 4.5% in women, compared with a placebo incidence of 0.3% in men and 0.9% in women); palpitations(1.4% in men, 3.3% in women, compared with a placebo incidence of 0.9% in men and 0.9% in women); and somrolence (1.3% in men, 1.6% in women, compared with a placebo incidence of 0.8% in men and 0.3% in women). The following events occurred in <1% but >0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, Dostural dizziness, postural hypotension; central and peripheral nervous system: hypoesthesia, paresthesia, tremor, vertgo; gastrointestinal: anorexia, constipation, dyspepsia,** dysphagia, diarrhea, flatulence, vomiting, gingival hyperplasia; general: asthenia,** back pain, hot flushes, malaise, pain, rigors, weight gain; musculoskeletal system: arthralgia arthrosis, muscle cramps,** myalgia; psychiatric: sexual dysfunction (male** and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization; respiratory system: dyspnea,** epistaxis; skin and appendages: pruritus,** rash,** rash erythematous, rash maculopapular; special senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus; urinary system: micturition frequency, micturition disorder, nocturia; autonomic nervous system: dry mouth, sweating increased; metabolic and nutritional: thirst; hemopoietic: purpura. The following events occurred in <0.1% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appeite, loose stools, coughing, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia. Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina. NORVASC therapy has not been associated with clinbally significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, creatinine or liver function ests. NORVASC has been used safely in patients with chronic obstructive pulmonary disease, well compensated congestive heart failure, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles. OVERDOSAGE: Single oral doses of 40 mg/kg and 100 ng/kg in mice and rats, respectively, caused deaths. A single oral dose of 4 mg/kg or higher in dogs caused a marked peripheral vasodilation and hypotension. Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of NORVASC is limited. Reports of intentional overdosage include a patient who ingested 250 mg and v»as asymptomatic and was not hospitalized; another (120 mg) was hospitalized, underwent gastric lavage and remained normotensive; the third (105 mg) was hospitalized and had hypotension (90/50 mmHg) which normalized following plasma expansion A patient who took 70 mg amlodipine and an unknown quantity of benzodiazepine in a suicide attempt,developed shock which was refractory to treatment and died the following day with abnormally high benzodiazepine plasma concentration. A case of accidental drug overdose has been documented in a 19 month old male who ingested 30 mg amlodipine (about 2 mg/kg). During the emergency room presentation, vital signs were stable with no evidence of hypotension, but a heart rate of 180 bpm. Ipecac was administered 3.5 hours after ingestion and on subsequentobseivation (overnight) no sequelae were noted. If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (sich as phenylephrine), should be considered with attention to circulating volume and urine output. Intravenous calcium cluconate may help to reverse the effects of calcium entry blockade. As NORVASC is highly protein bound, hemodiáysis is not likely to be of benefit. * Based on patient weight of 50 kg. **These events occurred in less than 1% in placebo controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies. U.S. Pharmaceuticals D1998, Pfizer Ine More detailed professional information available on request. Revised June 1996 Downloaded from www.ccjm.org on September 5, 2014. For personal use only. All other uses require permission.
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