Dosing Tips

✽ Generally given in one-third to one-sixth the dose of gabapentin

• If pregabalin is added to a second sedating agent, such as another anticonvulsant, a benzodiazepine, or an opiate, the titration period should be at least a week to improve tolerance to sedation

• Most patients need to take pregabalin only twice daily

• At the high end of the dosing range, tolerability may be enhanced by splitting dose into 3 or more divided doses

• For intolerable sedation, can give most of the dose at night and less during the day

• To improve slow-wave sleep, may only need to take pregabalin at bedtime

• May be taken with or without food

Overdose

• No fatalities

Long-Term Use

• Safe

Habit Forming

• No

How to Stop

• Taper over a minimum of 1 week

• Epilepsy patients may seize upon withdrawal, especially if withdrawal is abrupt

• Discontinuation symptoms uncommon

Pharmacokinetics

• Pregabalin is not metabolized but excreted intact renally

• Elimination half-life approximately 5–7 hours

Drug Interactions

• Pregabalin has not been shown to have significant pharmacokinetic drug interactions

• Because pregabalin is excreted unchanged, it is unlikely to have significant pharmacokinetic drug interactions

• May add to or potentiate the sedative effects of oxycodone, lorazepam, and alcohol

Other Warnings/Precautions

• Dizziness and sedation could increase the chances of accidental injury (falls) in the elderly

• Increased incidence of hemangiosarcoma at high doses in mice involves platelet changes and associated endothelial cell proliferation not present in rats or humans; no evidence to suggest an associated risk for humans

• Warn patients and their caregivers about the possibility of activation of suicidal ideation and advise them to report such side effects immediately

Do Not Use

• If there is a proven allergy to pregabalin or gabapentin

• If patient has a problem of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption

Pregabalin: special populations Renal Impairment

• Pregabalin is renally excreted, so the dose may need to be lowered

• Dosing can be adjusted according to creatinine clearance, such that patients with clearance below 15 mL/min should receive 25–75 mg/day in 1 dose, patients with clearance between 15–29 mL/min should receive 25–150 mg/day in 1–2 doses, and patients with clearance between 30–59 mL/min should receive 75–300 mg/day in 2–3 doses

• Starting dose should be at the bottom of the range; titrate as usual up to maximum dose

• Can be removed by hemodialysis; patients receiving hemodialysis may require a supplemental dose of pregabalin following hemodialysis (25–100 mg)

Hepatic Impairment

• Dose adjustment not necessary

Cardiac Impairment

• No specific recommendations

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more susceptible to adverse effects

Children and Adolescents

• Safety and efficacy have not been established

• Use should be reserved for the expert

Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• Antiepileptic Drug Pregnancy Registry: (888) 233–2334

• Taper drug if discontinuing

• Seizures, even mild seizures, may cause harm to the embryo/fetus

Breast Feeding

• Unknown if pregabalin is secreted in human breast milk, but all psychotropics assumed to be secreted in breast milk

✽ Recommended either to discontinue drug or bottle feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects

• If infant becomes irritable or sedated, breast feeding or drug may need to be discontinued

PREGABALIN: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• First-line for diabetic peripheral neuropathy

• Fibromyalgia

• Anxiety disorders

• Sleep

• Has relatively mild side effect profile

• Has few pharmacokinetic drug interactions

• More potent and probably better tolerated than gabapentin

Potential Disadvantages

• Requires 2–3 times a day dosing

• Not approved for anxiety disorders in the U.S.

• Not approved for fibromyalgia in Europe

Primary Target Symptoms

• Seizures

• Pain

• Anxiety

Pearls

✽ First treatment approved for fibromyalgia

✽ One of the first treatments approved for neuropathic pain associated with diabetic peripheral neuropathy

• Also approved in postherpetic neuralgia

• Improves sleep disruption as well as pain in patients with painful diabetic peripheral neuropathy or postherpetic neuralgia

• Improves sleep disruption as well as pain associated with fibromyalgia

• Well studied in epilepsy, peripheral neuropathic pain, and generalized anxiety disorder (GAD), and actually approved for GAD in Europe

✽ Off-label use for generalized anxiety disorder, panic disorder, and social anxiety disorder may be justified in the U.S.

• May have uniquely robust therapeutic actions for both the somatic and the psychic symptoms of generalized anxiety disorder

✽ Off-label use as an adjunct for bipolar disorder may not be justified

✽ One of the few agents that enhances slow-wave delta sleep, which may be helpful in chronic neuropathic pain syndromes

• Pregabalin is generally well tolerated, with only mild adverse effects

✽ Although no head-to-head studies, appears to be better tolerated and more consistently efficacious at high doses than gabapentin

✽ Drug absorption and clinical efficacy may be more consistent at high doses for pregabalin compared to gabapentin because of the higher potency of pregabalin and the fact that, unlike gabapentin, it is transported by more than one transport system

Suggested Reading

Lauria-Horner BA, Pohl RB. Pregabalin: a new anxiolytic. Expert Opin Investig Drugs 2003;12:663–72.

Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009;8(3):CD007076.

Stahl SM. Anticonvulsants and the relief of chronic pain: pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels. J Clin Psychiatry 2004;65:596–7.

Stahl SM. Anticonvulsants as anxiolytics, part 2: Pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels. J Clin Psychiatry 2004;65:460–1.

Stahl SM, Eisenach JC, Taylor CP, Cheung RY, Thorpe A, Clair A. The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacologic activities. Trends Pharmacological Sci 2013;34(6):332–9.

PROPRANOLOL

PROPRANOLOL: THERAPEUTICS

Brands

• Inderal

• Inderal LA

• InnoPran XL

see index for additional brand names

Generic?

Yes

Class

• Beta blocker, antihypertensive

Commonly Prescribed for

(bold for FDA approved)

• Migraine prophylaxis

• Essential tremor

• Hypertension

• Angina pectoris due to coronary atherosclerosis

• Cardiac arrhythmias (including supraventricular arrhythmias, ventricular tachycardia, digitalis intoxication)

• Myocardial infarction

• Hypertrophic subaortic stenosis

• Pheochromocytoma

• Akathisia (antipsychotic induced)

• Parkinsonian tremor

• Violence, aggression

• PTSD, prophylactic

• Generalized anxiety disorder

• Prevention of variceal bleeding

• Congestive heart failure

• Tetralogy of Fallot

• Hyperthyroidism (adjunctive)