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Pain Medications: Dosage and Indications

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Pain Medications: Dosage and Indications

Primary Care of Veterans with HIV

Drug Tables

April 2009; Last reviewed/updated: October 28, 2011

Contents

Pain Medications: Dosage and Indications
References

Please refer to Osteoarthritis, Low Back Pain, Peripheral Neuropathy

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Pain Medications: Dosage and Indications

Medication	Standard Dosage	Comments
* PI or other strong CYP3A4 inhibitors, eg, clarithromycin, ketoconazole, itraconazole, telithromycin, and neafazodone Abbreviations: CrCl = creatinine clearance; GI = gastrointestinal; HIV-SN = HIV sensory neuropathy; LBP = low back pain; OA = osteoarthritis; PN = peripheral neuropathy; TCAs = tricyclic antidepressants
Acetaminophen	1 g Q6H PRN or 650 mg Q4H PRN Maximum dosage: 4 g per 24 hours or 2 g per 24 hours in patients with comorbid liver disease	First-line analgesia in noninflammatory mild OA, LBP, mild PN because of safety profile Possible adverse effects: hepatotoxicity (especially if taken with alcohol), nephrotoxicity (with chronic overdose): monitor liver and renal function when using maximal dosages Use caution and consider reducing total dosage for patients with comorbid liver disease or excessive alcohol intake
NSAIDs	Ibuprofen 600-800 mg TID PRN for pain Take with food Schedule around the clock for inflammatory condition (eg, inflammatory OA) or persistent symptoms Can titrate up as tolerated and based on risks to 800 mg TID Maximum dosage: 3,200 mg/day in divided doses or 1,800 mg/day for patients at increased risk of adverse effects Alternative NSAIDs Naproxen: 250-500 mg BID Sulindac: 150-200 mg BID Celecoxib: 200 mg QD Meloxicam: 7.5 mg QD For chronic pain, use for 2 weeks at initial dosage and reevaluate efficacy; titrate up as needed and if safe; if not effective after a 4-week trial, consider changing NSAID, or adding or changing to another intervention	For persistent noninflammatory and inflammatory OA, LBP, mild PN Possible adverse effects: GI bleeding, abdominal pain, rash and hypersensitivity, renal and hepatic impairment, platelet aggregation abnormalities Avoid use in patients with peptic ulcer disease or cirrhosis Avoid ibuprofen in patients with history of aspirin-induced asthma Increased bleeding risk with concurrent warfarin; if used, monitor closely Increased risk of renal impairment in patients on diuretics and those with baseline renal dysfunction, congestive heart failure, or cirrhosis To minimize risks, use the lowest effective dosage and try to use for short periods of time COX-2 inhibitors, such as celecoxib, have higher risk of cardiovascular events but fewer GI side effects than nonselective COX inhibitors Indomethacin is associated with increased joint destruction; avoid using for OA or LBP
Antidepressants: TCAs and others	Amitriptyline Start at 10-25 mg QHS; titrate upward every 3 days by 25 mg to achieve symptom relief, if tolerated; maximum daily dosage is 150 mg (use lower dosages for older patients) Nortriptyline Start at 10-25 mg QHS; titrate upward every 3 days by 25 mg to achieve symptom relief, if tolerated; maximum daily dosage is 150 mg (use lower dosages for older patients)	Consider for patients with comorbid depression Consider for neuropathic pain; also as an adjunct in any type of LBP unresponsive to acetaminophen and NSAIDs Small studies of PN have shown limited or negative results with antidepressants Drug interactions: RTV and other PIs may increase the level of TCAs; start at low dosage, increase slowly Monitor serum TCA levels to avoid cardiotoxicity at higher dosage levels Possible TCA adverse effects: anticholinergic (dry mouth, dizziness, constipation, urinary retention, blurred vision, orthostatic hypotension), extrapyramidal symptoms, incoordination; risk of cardiac conduction abnormalities and overdose at higher dosages For neuropathic pain, other potential agents include venlafaxine and duloxetine; these are inadequately studied in people with HIV infection or show limited efficacy
Anticonvulsants	Gabapentin: start at 300 mg QHS; may increase every few days, as tolerated, to achieve symptom relief; first increase to BID, then TID, then increase by 300 mg per dose to maximum of 1,200 mg TID Pregabalin: start at 25-50 mg TID; may increase by 25-50 mg per dose every few days as tolerated to achieve symptom relief; maximum dosage: 200 mg TID Lamotrigine: start at 25 mg every other day; titrate slowly to 200 mg BID over the course of 6-8 weeks	Consider for PN Gabapentin: considered first-line for HIV-SN (See Peripheral Neuropathy) Common adverse effects include nausea, constipation, fatigue, somnolence, dizziness, truncal ataxia, weight gain To discontinue, taper over course of ≥7 days Pregabalin: sometimes better tolerated than gabapentin Uncertain efficacy in HIV-related PN Possible adverse effects include somnolence, constipation, dizziness, ataxia, and weight gain To discontinue, taper over course of ≥7 days Lamotrigine: has shown the greatest efficacy in clinical trials for HIV-SN Possible adverse effects: rash (including Stevens-Johnson syndrome), cytopenias, dizziness To discontinue, taper slowly Drug interactions: LPV/r may decrease lamotrigine levels; may need to increase lamotrigine dosage for therapeutic effect
Muscle relaxants (nonbenzo- diazepines)	Cyclobenzaprine (Flexeril) 5-10 mg TID; start with 5 mg doses for elderly patients and those with hepatic impairment; maximum dosage is 30 mg per 24 hours Baclofen 5-10 mg TID or QID; start with 5 mg doses for elderly patients and those with renal impairment; maximum dosage is 80 mg QD in divided doses	May be useful as adjunctive therapy for acute back pain but not recommended for chronic or subacute back pain Common adverse effects include drowsiness, dry mouth, and dizziness Severe adverse effects include arrhythmias, altered mental status, and seizures
Opiate analgesics	Options include: Tramadol (not a typical opiate; exact mechanism of action is unknown; acts in part as a central opioid agonist) Start with 50 mg QAM PRN pain, titrate upward by 50 mg/day every 3 days to 50 mg Q6H Maximum dosage: 400 mg/day, or 300 mg/day if >70 years of age; to discontinue, taper dosage in the same way In renal insufficiency with CrCl <30, reduce dose frequency to Q12H, and maximum dosage to 200 mg/day Weak opioids Codeine 15-30 mg every 4-6 hours; titrate up by 15 mg every 2-3 days to achieve pain relief, if tolerated Maximum dose: 60 mg; take with food Hydrocodone + acetaminophen 5 mg/500 mg fixed-dose tablet, 1-2 tablets Q6H PRN pain Maximum dosage: 12 tablets per 24 hours; 6 tablets for elderly patients and those with liver disease Oxycodone + acetaminophen 5 mg/325 mg fixed-dose tablet (other dosages available), 1-2 tablets Q6H PRN pain Maximum dosage: 12 tablets per 24 hours; 6 tablets for elderly patients and those with liver disease Strong opioids Morphine (immediate release) 10-30 mg every 3-4 hours PRN pain Morphine (sustained release) 15-30 mg Q12H as scheduled doses; if pain control is inadequate, consider dosing Q8H; may titrate up by 15-30 mg PRN pain Oxycodone (immediate release) 5-30 mg Q4H PRN pain Oxycodone (sustained release) 10 mg Q12H as scheduled doses; titrate up by 10-20 mg PRN; monitor carefully Methadone Consult with pharmacist Hydromorphone 2-4 mg Q4H PRN Fentanyl transdermal 12-100 mcg patch Q72H; a small proportion of patients will need dosing Q48H to maintain a stable blood level Appropriate only for patients already on stable dosage of other opiates; start at equianalgesic (or lower) dosage; consult with pharmacist; use for chronic severe pain	Use opioids for patients who have severe pain refractory to other interventions (pharmacologic or nonpharmacologic) or who cannot receive those interventions Start with weak opioids, assess safety, efficacy, and usage; titrate up and move to stronger opioids as needed Use the lowest effective dosage Use opioids cautiously in elderly patients If needed for acute flares, try to limit use to a designated short period of time If needed for chronic pain, try to use a sustained-release opioid (eg, sustained-release morphine) around the clock, plus shorteracting opioids (eg, hydrocodone) for breakthrough pain as needed Opioid therapy for chronic pain should use a fixed-dose schedule, not PRN dosing Methadone may have utility for neuropathic pain owing to its action on NMDA receptors; start at low dosage and titrate slowly because of its long half-life; consult with pharmacist Risk of dependence, overdose (accidental or deliberate); monitor closely Adverse effects include oversedation, hypotension and respiratory depression, central nervous system stimulation or somnolence, dizziness, constipation, nausea, pruritus Codeine and morphine can cause urticarial reactions (hives) For patients with renal and hepatic impairment, use low dosages and monitor carefully When prescribing opioids, remember to also give treatment for constipation (docusate and senna) Note that tramadol 37.5 mg + acetaminophen 325 mg has shown pain relief equivalent to codeine 30 mg + acetaminophen 325 mg but with fewer adverse effects (major adverse effect: headache) Chronic opioid therapy should incorporate an opioid use agreement that includes functional goals for outcome, not reduction of pain intensity alone
Topical anesthetics	Capsaicin 0.025% or 0.075% cream; apply to skin over affected joint(s) or limb TID-QID High-dose capsaicin topical dermal patch; apply for 30-90 minutes Lidocaine dermal patch 5% Apply 1-3 patches over affected area for 12 hours QD; must be removed for 12 hours	Capsaicin For noninflammatory and inflammatory OA, HIV-SN For OA or neuropathy, apply to skin over affected joint or area May take several days to achieve pain relief; initial application usually accompanied by sensation of heat or burning For neuropathy, a single capsaicin patch application can provide pain relief for up to 12 weeks Lidocaine Topical lidocaine may be used for neuropathic pain, but for HIV-SN it has not shown significant benefit over placebo, and is expensive; consider brief trial in patients with incomplete pain relief on other therapies
Colchicine	0.6 mg BID	For inflammatory OA with refractory symptoms Avoid use for patients with renal or hepatic disease Use in conjunction with NSAIDs Consider for patients with refractory inflammatory OA, as many have calcium pyrophosphate crystals in the synovial fluid If used with a PI*: For acute gout: reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later. Dose not to be repeated earlier than 3 days. For gout prophylaxis: reduce colchicine dosage to 0.3 mg QD (if on 0.6 mg BID prior to PI therapy) or reduce colchicine dose to 0.3 mg QOD (if on 0.6 mg QD prior to PI therapy).

References

McNicholl I. HIV InSite Database of Antiretroviral Drug Interactions. San Francisco: UCSF Center for HIV Information.
Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Rockville, MD: Department of Health and Human Services; January 10, 2011.
Also see product labeling for the individual ARVs.