eizures, the drug should be discontinued.
Visual disturbance
Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.
Prescribing and dispensing
The least amount of Elvanse Adult feasible should be prescribed or dispensed in order to minimise the risk of possible overdose by the patient.
Use with other sympathomimetic drugs
Elvanse Adult should be used with caution in patients who use other sympathomimetic drugs (see section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
In vitro enzyme inhibition
Lisdexamfetamine dimesylate was not an in vitro inhibitor of the major human CYP450 isoforms (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) in human hepatic microsomal suspensions, nor was it an in vitro inducer of CYP1A2, CYP2B6 or CYP3A4/5 in cultured fresh human hepatocytes. Lisdexamfetamine dimesylate was not an in vitro substrate for P-gp in MDCKII cells nor an in vitro inhibitor of P-gp in Caco-2 cells and is therefore unlikely to be involved in clinical interactions with drugs transported by the P-gp pump.
An in vivo human study of lisdexamfetamine dimesylate did not result in any clinically meaningful effect on the pharmacokinetics of drugs metabolized by CYP1A2, CYP2D6, CYP2C19, or CYP3A.
Agents whose blood levels may be impacted by Elvanse Adult
Extended release guanfacine: In a drug interaction study, administration of an extended release guanfacine in combination with Elvanse Adult induced a 19% increase in guanfacine maximum plasma concentrations, whereas, exposure (area under the curve; AUC) was increased by 7%. These small changes are not expected to be clinically meaningful. In this study, no effect on dexamfetamine exposure was observed following co-administration of extended release guanfacine and Elvanse Adult.
Extended release venlafaxine: In a drug interaction study, administration of 225 mg extended release venlafaxine, a CYP2D6 substrate, in combination with 70 mg Elvanse Adult induced a 9% decrease in the Cmax and 17% decrease in the AUC for the primary active metabolite o- desmethylvenlafaxine and a 10% increase in Cmax and 13% increase in AUC for venlafaxine.
Dexamfetamine may be a weak inhibitor of CYP2D6. Lisdexamfetamine has no effect on the AUC and Cmax of the composite of venlafaxine and o-desmethylvenlafaxine. These small changes are not expected to be clinically meaningful. In this study, no effect on dexamfetamine exposure was observed following co-administration of extended release venlafaxine and Elvanse Adult.
Agents and conditions that alter urinary pH and impact the urinary excretion and half-life of amfetamine
Ascorbic acid and other agents and conditions ( thiazide diuretics, diets high in animal protein, diabetes, respiratory acidosis) that acidify urine increase urinary excretion and decrease the half-life of amfetamine. Sodium bicarbonate and other agents and conditions (diets high in fruits and vegetables, urinary tract infections and vomiting) that alkalinise urine decrease urinary excretion and extend the half-life of amfetamine.
Monoamine oxidase inhibitors
Amfetamine should not be administered during or within 14 days following the administration of monoamine oxidase inhibitors (MAOI) because it can increase the release of norepinephrine and other monoamines. This can cause severe headaches and other signs of hypertensive crisis. A variety of toxic neurological effects an |
