DYANAVEL XR 20
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DYANAVEL XR 20 (DYANAVEL XR 20).
DYANAVEL XR is a central nervous system (CNS) stimulant. The mode of action is primarily through blockade of the reuptake of norepinephrine and dopamine into the presynaptic neuron, increasing their levels in the extraneuronal space. It also releases these monoamines from storage sites. The dextroamphetamine component is more potent than amphetamine in inhibiting norepinephrine reuptake, while the amphetamine component is more potent in inhibiting dopamine reuptake.
| Metabolism | Amphetamine is metabolized primarily by CYP2D6 and also by CYP2C19 and CYP3A4 via deamination, oxidation, and conjugation. The active metabolites include 4-hydroxyamphetamine and norephedrine. Genetic polymorphisms in CYP2D6 may affect metabolism and drug levels. |
| Excretion | Renal: 90% (unchanged drug and metabolites, primarily hippuric acid). Fecal/biliary: <1%. |
| Half-life | Terminal elimination half-life: 6-8 hours (stable metabolite). Clinical context: Twice-daily dosing typical due to pharmacokinetic profile; extended half-life compared to immediate-release amphetamine. |
| Protein binding | 15-40% bound to albumin. |
| Volume of Distribution | 3-5 L/kg (indicates extensive tissue distribution; crosses blood-brain barrier). |
| Bioavailability | Oral (extended-release): 95% (high bioavailability; minimal first-pass metabolism). |
| Onset of Action | Oral: 0.5-1 hour (extended-release formulation with bimodal release). |
| Duration of Action | 12 hours (based on pharmacokinetic profile and clinical efficacy; sustained effect throughout day). |
Initial 20 mg orally once daily in the morning, with or without food; may increase by 10 mg weekly to maximum 60 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 15-29 mL/min: maximum 40 mg/day; GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: not recommended. |
| Pediatric use | Ages 6-17: initial 10 mg once daily; may increase by 5-10 mg weekly to max 30 mg/day for ages 6-12, max 40 mg/day for ages 13-17. |
| Geriatric use | Initiate at 10 mg once daily; lower doses may be required due to renal function decline; monitor for cardiac effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DYANAVEL XR 20 (DYANAVEL XR 20).
| Breastfeeding | Amphetamines are excreted into human milk. The milk-to-plasma concentration ratio for amphetamine is approximately 1.8 to 5.9. A nursing infant would receive 4-10% of the maternal weight-adjusted dose. There are reports of irritability, poor feeding, and decreased weight gain in infants exposed to amphetamines via breast milk. The manufacturer recommends discontinuing nursing or the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Pregnancy Category C. There is no adequate and well-controlled study in pregnant women. In animal reproduction studies, amphetamine (dextroamphetamine/amphetamine) at doses up to 41 times the maximum recommended human dose of 20 mg/day (based on mg/m²) produced no teratogenic effects; however, increased neonatal mortality and reduced growth were observed at maternally toxic doses. In humans, retrospective studies have reported a higher incidence of premature delivery, low birth weight, and withdrawal symptoms (e.g., dysphoria, agitation, lassitude) in neonates exposed to amphetamines during the third trimester. There is also a potential risk for cardiovascular malformations if used in the first trimester. Therefore, the drug should be used only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
DYANAVEL XR has a high potential for abuse and dependence. Prolonged use may lead to drug dependence. Misuse may cause sudden death or serious cardiovascular events. It should be prescribed cautiously, especially in patients with a history of substance abuse.
| Serious Effects |
["Hypersensitivity to amphetamine or any component of the formulation.","Concurrent use or within 14 days of monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crisis.","Hyperthyroidism.","Agitated states.","Glaucoma.","History of drug abuse.","Cardiovascular disease: Moderate to severe hypertension, advanced arteriosclerosis, symptomatic coronary artery disease, structural heart abnormalities, cardiomyopathy, serious arrhythmias, or other serious cardiac conditions."]
| Precautions | ["Serious cardiovascular events: Sudden death, stroke, and myocardial infarction have been reported, especially in patients with structural cardiac abnormalities or other serious heart problems.","Blood pressure and heart rate increase: Monitor vital signs regularly.","Psychiatric adverse events: May exacerbate pre-existing psychosis, mania, or aggression; caution in patients with bipolar disorder or history of psychosis.","Seizures: May lower seizure threshold; use cautiously in patients with seizure disorders.","Peripheral vasculopathy: Including Raynaud's phenomenon; monitor for digital changes.","Serotonin syndrome: Risk when co-administered with serotonergic drugs.","Growth suppression: Long-term use may slow growth in children; monitor height and weight."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate, especially during dose titration. Observe for signs of excessive central nervous system stimulation (e.g., insomnia, irritability, agitation). In the fetus/neonate, monitor for signs of prematurity, low birth weight, and withdrawal symptoms such as dysphoria, agitation, and lassitude. Consider fetal growth ultrasound if clinically indicated due to concerns about intrauterine growth restriction. |
| Fertility Effects | In animal studies, amphetamine at doses up to 41 times the human dose did not impair fertility in males or females. Human data are insufficient; however, amphetamines may be associated with changes in libido or menstrual irregularities. No definitive evidence of impaired fertility in humans. |