PEMOLINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PEMOLINE (PEMOLINE).
Pemoline is a central nervous system stimulant that enhances dopaminergic and noradrenergic transmission by blocking the reuptake of dopamine and norepinephrine at the synaptic cleft. It also has mild monoamine oxidase inhibitory activity.
| Metabolism | Pemoline is extensively metabolized in the liver via hydroxylation and conjugation, primarily by cytochrome P450 enzymes, though specific isoenzymes are not well-defined. |
| Excretion | Pemoline is primarily excreted renally as unchanged drug (40-50%) and metabolites; approximately 20-30% is excreted in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is 8-12 hours in children; 12-16 hours in adults. Steady-state is reached within 2-3 days. |
| Protein binding | Approximately 50-60% bound to plasma proteins (albumin). |
| Volume of Distribution | Vd ~1-2 L/kg; indicates extensive tissue distribution, particularly to brain and liver. |
| Bioavailability | Oral bioavailability is approximately 100%; first-pass metabolism is negligible. |
| Onset of Action | Oral: 30-60 minutes; peak effect at 2-4 hours. |
| Duration of Action | Duration of action is 6-8 hours after a single oral dose; sustained effects with repeated dosing due to accumulation. |
Oral, 37.5 mg once daily in the morning; may increase by 18.75 mg weekly to a maximum of 112.5 mg/day (divided into 2 doses if total dose > 75 mg).
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with creatinine clearance < 50 mL/min. For CrCl 50-80 mL/min: dose at 50% of normal. No data for dialysis. |
| Liver impairment | Contraindicated in Child-Pugh Class B or C. For Child-Pugh Class A: use caution, maximum dose 56.25 mg/day. |
| Pediatric use | Children ≥6 years: initial oral 37.5 mg once daily in the morning; increase by 18.75 mg increments weekly to maximum 112.5 mg/day (divided if >75 mg). Not recommended for children <6 years. |
| Geriatric use | Start at 18.75 mg once daily in the morning; increase slowly by 18.75 mg every 2 weeks; maximum 75 mg/day. Monitor for renal function and cardiovascular effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PEMOLINE (PEMOLINE).
| Breastfeeding | Pemoline is excreted into human breast milk. The milk-to-plasma (M/P) ratio is unknown. Due to potential for serious adverse reactions in nursing infants, including insomnia, irritability, and weight loss, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Pemoline is an oxazolidine derivative CNS stimulant. Human data are limited, but animal studies have shown embryotoxicity and teratogenicity at high doses. There are no adequate and well-controlled studies in pregnant women. Avoid use in first trimester if possible. Second and third trimester risks include potential for adverse effects on fetal growth and CNS development. Use only if potential benefit outweighs unknown risks. |
■ FDA Black Box Warning
WARNING: LIVER TOXICITY. Pemoline is associated with life-threatening hepatic failure. It should not be used as first-line therapy for ADHD. Patients should be monitored for signs of liver injury.
| Serious Effects |
["Hypersensitivity to pemoline or any component","Pre-existing liver disease or hepatic dysfunction","Glaucoma","Motor tics or Tourette syndrome (or family history)","Concurrent use with monoamine oxidase inhibitors (MAOIs)","Marked anxiety, tension, or agitation"]
| Precautions | ["Hepatic failure: Monitor liver function tests before and during therapy; discontinue if elevated","Growth suppression: May cause temporary growth retardation in children","Psychiatric effects: May exacerbate psychosis, tics, or Tourette syndrome","Seizures: Use with caution in patients with seizure disorders","Cardiovascular effects: Monitor blood pressure and heart rate"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and weight regularly. Assess for signs of hepatotoxicity (LFTs) due to pemoline's association with liver failure. Monitor fetal growth and development via ultrasound, and consider fetal echocardiography if maternal hypertension develops. |
| Fertility Effects | Pemoline may impair fertility in both males and females based on animal studies showing reduced pregnancy rates and testicular changes. Human data are insufficient. |