Friday, July 21, 2023

gabapentin (ga-ba-pen-tin) Gralise, Horizant, Neurontin

 Indications

Partial seizures (adjunct treatment) (immediate-release

only). Postherpetic neuralgia. Restless legs syndrome

(Horizant only). Unlabeled Use: Neuropathic

pain. Prevention of migraine headache. Bipolar

disorder. Anxiety. Diabetic peripheral neuropathy.

Action

Mechanism of action is not known. May affect transport

of amino acids across and stabilize neuronal membranes.

Therapeutic Effects: Decreased incidence

of seizures. Decreased postherpetic pain. Decreased leg

restlessness.

Pharmacokinetics

Absorption: Well absorbed after oral administration

by active transport. At larger doses, transport becomes

saturated and absorptionp(bioavailability ranges from

60% for a 300-mg dose to 35% for a 1600-mg dose).

Distribution: Crosses blood-brain barrier; enters

breast milk.

Metabolism and Excretion: Eliminated mostly by

renal excretion of unchanged drug.

Half-life: Adults—5–7 hr (normal renal function);

up to 132 hr in anuria; Children—4.7 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO-IR rapid 2–4 hr 8 hr

PO-SR unknown 5–8 hr 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity.

Use Cautiously in: All patients (mayqrisk of suicidal

thoughts/behaviors); Renal insufficiency (pdose

and/orqdosing interval if CCr 60 mL/min); OB: Pregnancy;

Pedi: Children 18 yr (sustained-/extended-release)

or 3 yr (immediate-release) (safety not established);

Lactation: Discontinue drug or bottle-feed;

Geri: May be more susceptible to toxicity due to age-relatedpin

renal function.

Adverse Reactions/Side Effects

CNS: SUICIDAL THOUGHTS, confusion, depression, dizziness,

drowsiness, sedation, anxiety, concentration difficulties

(children), emotional lability (children), hostility,

hyperkinesia (children), malaise, vertigo,

weakness. EENT: abnormal vision, nystagmus. CV:

hypertension. GI: weight gain, anorexia, flatulence,

gingivitis. MS: RHABDOMYOLYSIS, arthralgia,qcreatine

kinase. Neuro: ataxia, altered reflexes, hyperkinesia,

paresthesia. Misc: ANAPHYLAXIS, ANGIOEDEMA, MULTIORGAN

HYPERSENSITIVITY REACTIONS.

Interactions

Drug-Drug: Antacids maypabsorption of gabapentin.

qrisk of CNS depression with other CNS depressants,

including alcohol, antihistamines, opioids,

and sedative/hypnotics. Mayphydrocodone levels.

Drug-Natural Products: Kava-kava, valerian,

or chamomile canqCNS depression.

Route/Dosage

The sustained-/extended-release formulations should

not be interchanged with the immediate-release products.

Epilepsy

PO (Adults and Children 12 yr): 300 mg 3 times

daily initially. Titration may be continued until desired

(range is 900–1800 mg/day in 3 divided doses; doses

should not be more than 12 hr apart). Doses up to

2400–3600 mg/day have been well tolerated.

PO (Children 5–12 yr): 10–15 mg/kg/day in 3 divided

doses initially titrated upward over 3 days to 25–

35 mg/kg/day in 3 divided doses; dosage interval

should not exceed 12 hr (doses up to 50 mg/kg/day

have been used).

PO (Children 3–4 yrs): 10–15 mg/kg/day in 3 divided

doses initially titrated upward over 3 days to 40

mg/kg/day in 3 divided doses; dosage interval should

not exceed 12 hr (doses up to 50 mg/kg/day have been

used).

Renal Impairment

PO (Adults and Children 12 yr): CCr 30–59 mL/

min—200–700 mg twice daily; CCr 15–29 mL/

min—200–700 mg once daily; CCr 15 mL/min—

100–300 mg once daily; CCr 15 mL/min—Reduce

daily dose in proportion to CCr.

Postherpetic Neuralgia

PO (Adults): Immediate-release—300 mg once

daily on first day, then 300 mg 2 times daily on second

day, then 300 mg 3 times/day on day 3, may then be titrated

upward as needed up to 600 mg 3 times/day;

Sustained-release (Gralise)—300 mg once daily on

first day, then 600 mg once daily on second day, then

900 mg once daily on days 3–6, then 1200 mg once

daily on days 7–10, then 1500 mg once daily on days

11–14, then 1800 mg once daily thereafter; Extendedrelease

(Horizant)—600 mg once daily in the morning

on days 1–3, then 600 mg twice daily thereafter.

Renal Impairment

PO (Adults): CCr 30–59 mL/min—200–700 mg

twice daily (immediate-release); 600–1800 mg once daily (sustained-release [Gralise]); 300 mg once daily

in the morning on days 1–3, then 300 mg twice daily

thereafter (mayqto 600 mg twice daily, as needed)

(extended-release [Horizant]); CCr 15–29 mL/

min—200–700 mg once daily (immediate-release);

sustained release (Gralise) not recommended; 300 mg

in the morning on days 1 and 3, then 300 mg once daily

in the morning thereafter (mayqto 300 mg twice daily,

as needed) (extended-release [Horizant]); CCr 15 mL/

min—100–300 mg once daily (immediate-release);

sustained release (Gralise) not recommended; CCr

15 mL/min—pdaily dose in proportion to CCr (immediate

release); sustained release (Gralise) not recommended;

300 mg every other day in the morning

(mayqto 300 mg once daily in the morning, as

needed) (extended-release [Horizant]); CCr 15 mL/

min (on hemodialysis)—300 mg after each dialysis

session (mayqto 600 mg after each dialysis session, as

needed) (extended-release [Horizant]).

Restless Legs Syndrome

PO (Adults): Extended-release (Horizant)—600

mg once daily at 5 PM.

Renal Impairment

(Adults): CCr 30–59 mL/min—300 mg once daily at

5 PM; mayqto 600 mg once daily at 5 PM as needed;

CCr 15–29 mL/min—300 mg once daily at 5 PM; CCr

15 mL/min—300 mg every other day; CCr 15 mL/

min (on hemodialysis)—Not recommended.

Neuropathic Pain (unlabeled use)

PO (Adults): 100 mg 3 times daily initially. Titrate

weekly by 300 mg/day up to 900–2400 mg/day (maximum:

3600 mg/day).

PO (Children): 5 mg/kg/dose at bedtime initially then

qto 5 mg/kg twice daily on day 2 and 5 mg/kg 3 times

daily on day 3. Titrate to effect up to 8–35 mg/kg/day

in 3 divided doses.

Availability (generic available)

Capsules: 100 mg, 300 mg, 400 mg. Cost: Generic—

100 mg $11.45/100, 300 mg $15.18/100, 400 mg

$12.36/100. Tablets: 600 mg, 800 mg. Cost: Generic—

600 mg $33.96/100, 800 mg $49.20/100. Extended-

release tablets (Horizant): 300 mg, 600

mg. Sustained-release tablets (Gralise): 300 mg,

600 mg. Cost: 300 mg $99.00/30, 600 mg $329.40/90.

Oral solution (cool strawberry anise flavor): 250

mg/5 mL. Cost: Generic—$148.91/470 mL.

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