You are in: eMedicine Specialties > Physical Medicine and Rehabilitation > MEDICAL DISEASES Chronic Pain SyndromeArticle Last Updated: Oct 26, 2005AUTHOR AND EDITOR INFORMATIONAuthor: Manish K Singh, MD, Assistant Professor, Pain Management, Department of Neurology, Drexel College of Medicine, Hahnemann University Hospital Manish K Singh is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Association of Physicians of Indian Origin, American Headache Society, American Medical Association, and American Society of Regional Anesthesia and Pain Medicine Coauthor(s): Jashvant Patel, MD, Medical Director, Department of Pain Medicine and Comprehensive Rehabilitation, Medical College of Pennsylvania Hahnemann University; Rollin M Gallagher, MD, MPH, Clinical Professor, Department of Psychiatry, Director, Center for Pain Medicine, University of Pennsylvania; Director, Pain Management Service, Philadelphia Veterans Affairs Medical Center Editors: Martin K Childers, DO, PhD, Associate Professor, Department of Neurology, Wake Forest University Health Services; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Richard Salcido, MD, Chairman, Erdman Professor of Rehabilitation, Department of Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine; Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center; Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers, Phoenix Author and Editor Disclosure Synonyms and related keywords: chronic benign pain syndrome, chronic intractable benign pain syndrome, CPS INTRODUCTIONBackgroundChronic pain syndrome (CPS) is a common problem that presents a major challenge to healthcare providers because of its complex natural history, unclear etiology, and poor response to therapy. CPS is a poorly defined condition. Most authors consider ongoing pain lasting longer than 6 months as diagnostic, and others have used 3 months as the minimum criterion. In chronic pain, the duration parameter is used arbitrarily. Some authors suggest that any pain that persists longer than the reasonable expected healing time for the involved tissues should be considered chronic pain. CPS is a constellation of syndromes that usually do not respond to the medical model of care. This condition is managed best with a multidisciplinary approach, requiring good integration and knowledge of multiple organ systems. PathophysiologyThe pathophysiology of CPS is multifactorial and complex and still is poorly understood. Some authors have suggested that CPS might be a learned behavioral syndrome that begins with a noxious stimulus that causes pain. This pain behavior then is rewarded externally or internally. Thus, this pain behavior is reinforced, and then it occurs without any noxious stimulus. Internal reinforcers are relief from personal factors associated with many emotions (eg, guilt, fear of work, sex, responsibilities). External reinforcers include such factors as attention from family members and friends, socialization with the physician, medications, compensation, and time off from work. Patients with several psychological syndromes (eg, major depression, somatization disorder, hypochondriasis, conversion disorder) are prone to developing CPS. FrequencyUnited StatesPain is the most common complaint that leads patients to seek medical care. Chronic pain is not uncommon. Approximately 35% of Americans have some element of chronic pain, and approximately 50 million Americans are disabled partially or totally due to chronic pain. Mortality/MorbidityCPS can affect patients in various ways. Major effects in the patient's life are depressed mood, fatigue, reduced activity and libido, excessive use of drugs and alcohol, dependent behavior, and disability out of proportion to impairment. RaceNo known predilection of CPS for any racial group has been described in the literature. SexChronic pain is reported more commonly in women. CLINICALHistoryBecause of the complex etiology and the frequent presence of associated disorders, a general and open-minded approach to the assessment of the patient is needed. Obtaining the history of patients whose symptoms suggest CPS is important. A thorough history is necessary for the physician to direct further evaluation and appropriate consultations and avoid repeating invasive and expensive procedures. A detailed review of the musculoskeletal, reproductive, gastrointestinal, urologic, and neuropsychological systems must be obtained. As needed, specific questions should be asked of particular patients, depending on their associated disorders.
PhysicalGood rapport, tolerance, and an open-minded approach are important when evaluating any patient with chronic pain. A good thorough systematic examination usually leads to an appropriate diagnosis and therapy. Patients often have Waddell signs. The disability is usually out of proportion to the impairment and the objective findings. Detailed examination of the musculoskeletal system is important. Examination of various other systems (eg, gastrointestinal, urologic, neurologic) also should be performed. CausesVarious neuromuscular, reproductive, gastrointestinal, and urologic disorders may cause or contribute to chronic pain. Sometimes multiple contributing factors may be present in a single patient.
DIFFERENTIALS[Lumbar Degenerative Disc Disease] Achilles Tendon Injuries and Tendonitis Adhesive Capsulitis Brachial Neuritis Carpal Tunnel Syndrome Cervical Disc Disease Cervical Myofascial Pain Cervical Spondylosis Cervical Sprain and Strain Complex Regional Pain Syndromes Fibromyalgia Lateral Epicondylitis Lumbar Facet Arthropathy Lumbar Spondylolysis and Spondylolisthesis Mechanical Low Back Pain Medial Epicondylitis Meralgia Paresthetica Mononeuritis Multiplex Morton Neuroma Myofascial Pain Neoplastic Brachial Plexopathy Neoplastic Lumbosacral Plexopathy Osteoarthritis Osteoporosis and Spinal Cord Injury Piriformis Syndrome Plantar Fasciitis Radiation-Induced Brachial Plexopathy Radiation-Induced Lumbosacral Plexopathy Rotator Cuff Disease Spasticity Thoracic Outlet Syndrome Traumatic Brachial Plexopathy Trochanteric Bursitis
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| Drug Name | Amitriptyline (Elavil) |
|---|---|
| Description | Analgesic for certain chronic and neuropathic pain. |
| Adult Dose | 25-100 mg/d PO hs; not to exceed 150 mg /d |
| Pediatric Dose | Children: 0.1 mg/kg PO hs; increase, as tolerated, over 2-3 wk to 0.5-2 mg/d hs Adolescents: 25-50 mg/d PO initially; increase gradually to 100 mg/d in divided doses |
| Contraindications | Documented hypersensitivity; patients who have taken MAOIs in past 14 d; has history of seizures, cardiac arrhythmias, glaucoma, and urinary retention |
| Interactions | Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in cardiac conduction disturbances, history of hyperthyroidism, or history of renal or hepatic impairment; avoid using in the elderly |
| Drug Name | Nortriptyline (Pamelor) |
|---|---|
| Description | Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS. Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action. |
| Adult Dose | 25-100 mg PO hs; not to exceed 200 mg/d |
| Pediatric Dose | Children: 0.1 mg/kg PO hs; increase, as tolerated, up to 0.5-2 mg/d hs Adolescents: 25-50 mg/d PO; gradually increase to 100 mg/d |
| Contraindications | Documented hypersensitivity; narrow-angle glaucoma; patients who have taken MAOIs in past 14 d |
| Interactions | Cimetidine may increase nortriptyline levels when used concurrently; nortriptyline may increase prothrombin time in patients stabilized with warfarin |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in cardiac conduction disturbances, history of hyperthyroidism, and history of renal or hepatic impairment; due to pronounced effects in cardiovascular system, best to avoid in elderly |
| Drug Name | Duloxetine (Cymbalta) |
|---|---|
| Description | Indicated for diabetic peripheral neuropathic pain. Potent inhibitor of neuronal serotonin and norepinephrine reuptake. |
| Adult Dose | 60 mg PO qd; may initiate with lower dose in patient unable to tolerate 60 mg/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; uncontrolled narrow-angle glaucoma; within 14 d of stopping MAO inhibitor use (do not initiate MAO inhibitors within 5 d of stopping duloxetine) |
| Interactions | Metabolized by CYP1A2 and CYP2D6; coadministration with drugs that inhibit CYP1A2 (eg, fluvoxamine, cimetidine, ciprofloxacin, enoxacin) may increase duloxetine blood levels and toxicity; coadministration with drugs that inhibit CYP2D6 (eg, paroxetine, fluoxetine, quinidine) may increase duloxetine blood levels and toxicity; duloxetine moderately inhibits CYP2D6 and may decrease elimination of CYP2D6 substrates (eg, tricyclic antidepressants, phenothiazines [eg, thioridazine], type 1C antiarrhythmics [eg, propafenone, flecainide]); coadministration with MAO inhibitors or triptans serotonin syndrome consisting of serious, sometimes fatal reactions that include hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes including extreme agitation, delirium, and coma (see contraindications) |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Observe closely for clinical worsening and suicidality when initiating treatment or following dosage change; gradually decrease dose when discontinuing, do not abruptly discontinue; caution with hepatic impairment or end-stage renal disease; recommended not to prescribe to patients with substantial alcohol use or evidence of chronic liver disease; may cause slight blood pressure increase; may activate mania or hypomania; common adverse effects include nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence and increased sweating; may cause serotonin syndrome (ie, changes in mental status [agitation, hallucinations, coma], autonomic instability [tachycardia, labile blood pressure, hyperthermia], neuromuscular abnormalities [hyperreflexia, incoordination], and/or gastrointestinal tract symptoms |
| Drug Name | Venlafaxine (Effexor) |
|---|---|
| Description | Inhibit neuronal serotonin and norepinephrine reuptake. In addition, causes beta-receptor down-regulation. May decrease pain in neuropathic pain and help with sleep and other mood disorders (depression or depressive symptoms). |
| Adult Dose | 5 mg PO qd initially; can be increased gradually to 50-150 mg PO bid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; patients taking MAO inhibitors or who have taken them within 14 days of initiating therapy |
| Interactions | Cimetidine, MAO inhibitors, sertraline, fluoxetine class I-C antiarrhythmics, TCAs, phenothiazine may increase the effects of venlafaxine |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Patients on this medication may experience hypertension; fatal reaction may occur if venlafaxine is taken concurrently with an MAO inhibitor; exercise caution in patients with cardiovascular disorders; the sustained release formulation should not be divided, crushed, or placed in water |
| Drug Name | Fluoxetine (Prozac) |
|---|---|
| Description | An atypical non-TCA with potent specific 5HT-uptake inhibition and fewer anticholinergic and cardiovascular adverse effects than TCAs. Consider as alternative to TCAs. |
| Adult Dose | 10 mg PO on waking; can be increased q2wk; not to exceed 60 mg/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; pregnancy and breastfeeding; severe renal or hepatic disease |
| Interactions | Increases toxicity of diazepam and trazodone by decreasing clearance; also increases toxicity of MAOIs and highly protein-bound drugs; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan); discontinue other serotonergic agents at least 2 wk prior to SSRIs |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in hepatic impairment and history of seizures; MAOIs should be discontinued at least 14 d before initiating fluoxetine therapy; anxiety, insomnia or drowsiness, tremor, anorexia, anorgasmia, and other sexual dysfunctions have been reported; nausea, flulike symptoms, and agitation that resolve within 1-2 wk also have been noted |
| Drug Name | Sertraline (Zoloft) |
|---|---|
| Description | An atypical non-TCA with potent specific 5HT-uptake inhibition and fewer anticholinergic and cardiovascular adverse effects than TCAs. Consider as alternative to TCAs. |
| Adult Dose | 50 mg/d PO initially; increase at weekly intervals after several weeks; not to exceed 200 mg/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; pregnancy and breastfeeding; severe renal or hepatic disease |
| Interactions | Serious potentially fatal reactions such as autonomic instability may occur with concurrent use of MAOIs; other antidepressants, phenothiazines, group IC antiarrhythmics, cimetidine, phenytoin, phenobarbital, digoxin, and warfarin |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in preexisting seizure disorders, recent myocardial infarction, unstable heart diseases, and hepatic or renal impairment; anxiety, insomnia or drowsiness, tremor, anorexia, anorgasmia, and other sexual dysfunctions have been reported; nausea, flulike symptoms, and agitation that resolve within 1-2 wk also have been noted |
| Drug Name | Paroxetine (Paxil) |
|---|---|
| Description | An atypical non-TCA with potent specific 5HT-uptake inhibition and fewer anticholinergic and cardiovascular adverse effects than TCAs. Consider as alternative to TCAs. |
| Adult Dose | 10 mg/d PO initially, then titrate upward; not to exceed 50 mg/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; pregnancy and breastfeeding; severe renal or hepatic disease |
| Interactions | Serious potentially fatal reactions such as autonomic instability may occur with concurrent use of MAOIs; other antidepressants, phenothiazines, group IC antiarrhythmics, cimetidine, phenytoin, phenobarbital, digoxin, and warfarin |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Anxiety, insomnia or drowsiness, tremor, anorexia, anorgasmia, and other sexual dysfunctions have been reported; nausea, flulike symptoms, and agitation that resolve within 1-2 wk also have been noted |
Certain antiepileptic drugs (eg, the GABA analogue gabapentin and pregabulin [Lyrica]) have proven helpful in some cases of neuropathic pain. Other anticonvulsant agents (eg, clonazepam, topiramate, lamotrigine, zonisamide, tiagabine) also have been tried in CPS.
| Drug Name | Gabapentin (Neurontin) |
|---|---|
| Description | Has anticonvulsant properties and antineuralgic effects; however, exact mechanism of action is unknown. Structurally related to GABA but does not interact with GABA receptors. |
| Adult Dose | 100-1200 mg PO tid |
| Pediatric Dose | <12 years: Not recommended >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids may significantly reduce bioavailability of gabapentin (administer at least 2 h following antacids); may increase norethindrone levels significantly |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in severe renal disease; abrupt withdrawal may precipitate seizures |
Used commonly for many pain syndromes. Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have sustained traumatic injuries.
| Drug Name | Oxycodone (OxyContin, OxyIR, Roxicodone) |
|---|---|
| Description | Long-acting opioids may be used in patients with CPS. Start with small dose, and if appropriate, gradually increase. |
| Adult Dose | 10-160 mg PO q12h |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; presence of intracranial lesion associated with impaired intracranial pressure (hydromorphone); patients receiving MAOIs or those who have recently used MAOIs; poor respiratory function (eg, COPD, cor pulmonale, emphysema, status asthmaticus, kyphoscoliosis) |
| Interactions | Phenothiazines may antagonize analgesic effects; MAOIs, general anesthesia, CNS depressants, and TCAs may increase toxicity |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in COPD, emphysema, and renal insufficiency |
| Drug Name | Fentanyl (Duragesic) |
|---|---|
| Description | Potent narcotic analgesic with much shorter half-life than morphine sulfate. DOC for conscious sedation analgesia. Ideal for analgesic action of short duration during anesthesia and during immediate postoperative period. Excellent choice for pain management and sedation with short duration (30-60 min). Easy to titrate. Easily and quickly reversed by naloxone. When using transdermal dosage form, most patients achieve pain control with 72-h dosing intervals; however, some patients require dosing intervals of 48 h. |
| Adult Dose | 25-100 mcg/h TD system q2-3d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; hypotension or potentially compromised airway that would cause difficulty in establishing rapid airway control |
| Interactions | Phenothiazines may antagonize analgesic effects of opiate agonists; TCAs may potentiate adverse effects of fentanyl when both drugs are used concurrently |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in hypotension, respiratory depression, constipation, nausea, emesis, and urinary retention; idiosyncratic reaction, known as chest wall rigidity syndrome, may require neuromuscular blockade in order to increase ventilation |
| Drug Name | Acetaminophen (Tylenol, Feverall, Aspirin Free Anacin) |
|---|---|
| Description | DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, who are pregnant, or who are taking oral anticoagulants. |
| Adult Dose | 650-1000 mg PO, initially; may repeat after 6h if necessary |
| Pediatric Dose | <3 years: Not established 3-6 years: 10 mg/kg PO; not to exceed 720 mg/d 6-12 years: 10 mg/kg PO; not to exceed 2.6 g/d >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; known G-6-PD deficiency |
| Interactions | Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Hepatotoxicity possible following various dose levels in those with chronic alcoholism; severe or recurrent pain or high or continued fever may indicate a serious illness; APAP is contained in many OTC products, and combined use with these products may result in cumulative APAP doses exceeding recommended maximum dose |
| Drug Name | Pregabalin (Lyrica) |
|---|---|
| Description | Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha2-delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures. |
| Adult Dose | 50 mg PO tid initially; if needed, may increase to 100 mg tid within 1 wk |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea with abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with renal impairment (ie, CrCl <60 mL/min); angioedema has been reported during postmarketing surveillance |
Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.
| Drug Name | Ibuprofen (Motrin, Advil, Ibuprin) |
|---|---|
| Description | DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. |
| Adult Dose | 400-800 mg PO q8h; not to exceed 3.2 g/d |
| Pediatric Dose | <6 months: Not established 6 months to 12 years: 4-10 mg/kg/dose PO tid/qid >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding |
| Interactions | Coadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy |
| Drug Name | Naproxen sodium (Anaprox, Naprelan, Naprosyn, Anaprox) |
|---|---|
| Description | For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis. |
| Adult Dose | 275 mg PO tid or 550 mg PO bid |
| Pediatric Dose | <2 years: Not established >2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d |
| Contraindications | Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency |
| Interactions | Coadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug |
Article Last Updated: Oct 26, 2005