| Note on dosing: For some of the drugs, the maximum daily doses specified may produce systemic concentrations that are associated with pharmacologic toxicities, particularly in patients with impaired end-organ function. For these, information about toxic concentrations for the drug and relevant metabolites are provided as follows: TDM Toxic: [analyte name], concentrations at which drug-related toxicities typically occur (specimen in which the concentration is measured). TDM, Therapeutic drug monitoring |
| Drug | Analgesic Indication | Dosing (see note above) | Special Considerations | Side Effects |
| Anticonvulsants |
| Carbamazepine | Trigeminal neuralgia Diabetic neuropathy | 300 mg TID orally Max. 300 mg QID orally | Obtain CBC and LFTs before administration Monitor for agranulocytosis | Somnolence, dizziness, gait disturbance |
| Note: TDM Toxic: carbamazepine (blood) ≥15 mg/L (≥64 μmol/L) |
| Gabapentin | Postherpetic neuralgia Diabetic neuropathy Migraine headaches | 300 mg TID orally Max. 1200 mg TID orally | Somnolence may require lower initial dosing Night-time dosing may facilitate sleep | Somnolence, diarrhea, mood swings, fatigue nausea, dizziness |
| Note: TDM Toxic: gabapentin (blood) ≥25 mcg/mL (≥25 mg/L) |
| Lamotrigine | HIV neuropathy Trigeminal neuralgia Cold-induced allodynia | 25–50 mg/day orally Max. 200 mg BID orally | Titrate slowly For pain refractory to phenytoin and carbamazepine Valproic acid reduces clearance | Rash, dizziness, ataxia, constipation, nausea, diplopia, somnolence |
| Note: TDM Toxic: not established. Be wary of lamotrigine (blood) >20 mcg/mL (>20 mg/L) |
| Oxcarbazepine | Trigeminal neuralgia | 300–600 mg/day orally Max. 2400 mg/day orally | Similar to carbamazepine with less-severe side effects | Skin sensitivity, hyponatremia |
| Phenytoin | Trigeminal neuralgia Diabetic neuropathy | 300 mg/day orally 1000 mg initial loading dose orally or intravenously | Weak to moderate analgesic effect Obtain CBC and LFTs before administration | Gingival hyperplasia, hirsutism |
Note: TDM Toxic: total phenytoin (blood) >20 mg/L (>79 μmol/L); TDM Toxic: free phenytoin (blood) ≥2.5 mg/L (≥9.9 μmol/L) Phenytoin is available in the United States generically in a variety of formulations and strengths for oral administration, including prompt-release capsules containing 100 mg phenytoin sodium (equivalent to 92 mg phenytoin); extended-release capsules containing 30 mg or 100 mg phenytoin sodium (equivalent to 27.6 mg and 92 mg phenytoin, respectively); extended-release capsules containing 200 mg or 300 mg phenytoin sodium (equivalent to 184 mg and 276 mg phenytoin, respectively); chewable tablets containing 50 mg phenytoin; and a liquid suspension containing 125 mg phenytoin/5 mL and ≤6% alcohol |
| Topiramate | Postthoracotomy Reflex sympathetic dystrophy Headaches, intercostal neuralgia | 25–50 mg/day orally Max. 200 mg BID orally | Prolonged use may cause renal calculi Absorption slowed by food | Anorexia, weight loss |
| Valproic acid | Migraine headaches Cluster headaches Tension headaches | 250 mg/day orally Max. 600 mg TID orally | Multiple drug interactions | CNS depression, hepatic, hematologic toxicity |
| Note: TDM Toxic: total valproic acid (blood) >120 mg/L (>832 >mol/L); TDM Toxic: free valproic acid (blood) >15 mg/L (>104
μmol/L) |
| Tricyclic Antidepressants |
Amitriptyline (Elavil, and many generic products) | Neuropathic pain Musculoskeletal pain | 10–25 mg orally at bedtime Max. 150 mg orally at bedtime | Take 10 hours before planned waking to decrease side effects | Dry mouth, sedation, cardiac arrhythmias, urinary retention |
| Note: TDM Toxic: amitriptyline (blood) ≥500 mcg/L (≥1805 nmol/L) |
Desipramine (Norpramin, and many generic products) | Neuropathic pain Musculoskeletal pain | 10–25 mg orally at bedtime Max. 50–100 mg orally at bedtime | Less sedative and anticholinergic effects than amitriptyline | Dry mouth, sedation, cardiac arrhythmias, urinary retention |
| Note: TDM Toxic: desipramine (blood) ≥500 mcg/L (≥1880 nmol/L) |
Nortriptyline (Pamelor, and many generic products) | Neuropathic pain Musculoskeletal pain | 10–25 mg orally at bedtime Max. 100–150 mg orally at bedtime | | Dry mouth, sedation, cardiac arrhythmias, urinary retention |
| Note: TDM Toxic: nortriptyline (blood) ≥500 mcg/L (≥1900 nmol/L) |
| Neuroleptic Agents |
| Olanzapine | Opioid-induced cognitive impairment | 2.5–5 mg/day orally Max 20 mg/day orally | Safer neuroleptic, with reduced extrapyramidal effects, drug interactions, and neutropenia | Agitation, headache, insomnia, somnolence |
| |
| NMDA (N-methyl-d-aspartate) Receptor Antagonists (a glutamate receptor) |
| Ketamine | Refractory neuropathic pain | 0.1–1.5 mg/kg per hour, intravenously Use as continuous infusion in hospice setting; or intermittently for less-severe pain | Poorly absorbed orally Do not use with increased ICP, hypertension, or psychosis Ketamine is hepatically metabolized Pharmacodynamic effects may be prolonged in patients with impaired liver function | Confusion, hallucinations |
| Methadone | Somatic pain Neuropathic pain | 2.5 mg QD or BID orally or intravenously | May reduce opioid tolerance | |
| Dextromethorphan polistirex oral suspension, extended-release equivalent to 30 mg dextromethorphan HBr/5 mL (Delsym) | Polyneuropathy | 15 mg BID orally Maximum dose can vary and is determined empirically | Slow-release dextromethorphan Product contains 0.26% alcohol | Pharmacokinetic interaction between dextromethorphan and serotonin reuptake inhibitors or MAO inhibitors may result in serotonin syndrome |
| Antiarrhythmics |
| Mexiletine | Refractory neuropathic pain | 50 mg TID orally Max. 10 mg/kg per day orally | May worsen preexisting cardiac arrhythmias. Do not use in second- and third-degree AV blocks Monitor ECG at high doses | Nausea, anxiety, dizziness |
| Note: TDM Toxic: mexiletine (blood) >2 mcg/mL (>11.2 μmol/L) |
| Lidocaine | Refractory neuropathic pain | Administer intravenously | Do not use with compromised cardiac contractility or conduction Avoid use of tricyclic antidepressants | |
| Note: TDM Toxic: lidocaine (blood) ≥6 mcg/mL (≥25.6 μmol/L) |
| Local/Cutaneous Anesthetics |
| Eutectic mixture of lidocaine 2.5% and prilocaine 2.5% (EMLA) | Peripheral neuropathy allodynia | Apply topically to intact skin QID and cover with an occlusive dressing (eg, OpSite film dressing; Smith & Nephew Inc., Memphis, TN) | | |
| Lidocaine patch 5% (Lidoderm) | Postherpetic neuralgia | Apply topically to intact skin for up to 12 hours every 24 hours | | |
| Topical Agents |
| Capsaicin | Peripheral neuropathy Arthropathy Mucositis | Apply topically to intact skin QID | | |
| Polyvinylpyrrolidone, sodium hyaluronate, and glycyrrhetinic acid bioadherent oral gel (Gelclair) | Mucositis | Dilute the contents of 1 Gelclair packet with 1–3 tablespoons (15–45 mL) tap water (or may be used undiluted); “swish” the product around the oral cavity or gargle with it for at least 1 minute, QID. The product is usually expectorated, but is harmless if swallowed | | |
| Corticosteroids |
| Dexamethasone | Oncologic emergency (spinal cord or nerve compression) Refractory neuropathic pain Increased ICP Organ distention Bone metastasis | 80–100 mg intravenously × 1, then 10–12 mg intravenously QID; or 1 mg–4 mg orally QID | Improves pain, nausea, appetite, and malaise Longer duration of action (36–72 hours) No mineralocorticoid effects (edema) Taper dosing to discontinue | Myopathy, delirium, depression |
| Prednisone | | 5–10 mg BID orally | Use to reduce myopathy Taper dose to discontinue Improves pain, nausea, and appetite | Hypotension, dry mouth, somnolence |
| α2-Adrenergic Agonists |
| Clonidine | Diabetic neuropathy Cancer-related neuropathy Chronic headache | 0.1 mg/day orally max. 2 mg/day orally; or Apply and replace topical patches to intact hairless skin every 7 days | Beneficial in less opioid-responsive patients May reduce opioid requirement | Hypotension, dry mouth, somnolence |
BID, twice per day; ICP, intracranial pressure; QD, once per day; QID, 4 times per day; TID, 3 times per day Reproduced, with permission, from Pereira D, St. Germaine D. Pharmacologic Adjuvant Therapy for Cancer Pain. In: Berger A, ed. Advances in Cancer Pain: A Bedside Approach. The Oncology Group, CMP Healthcare Media, Manhasset, NY, ©2004 |