Stimulant-like Effects: Modafinil vs Adderall The cognitive enhancement that comes from using modafinil pills does not happen in the same way as when using Adderall. The MCMs included congenital torticollis (n=4), hypospadias (n=2), congenital heart defects (n=3). Administer modafinil in the morning to get maximal effects during waking hours and to avoid possible interference with nocturnal sleep.May be administered with food. If these drugs are used together, monitor patients for a decrease in clinical effects; patients should report breakthrough bleeding to their prescriber. If these drugs are used together, monitor patients for a decrease in clinical effects. Coadministration of a CYP3A4 inducer, like modafinil, may decrease systemic concentrations of romidepsin. Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with modafinil can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. Background Modafinil is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Nothing is known about its effect on hormone secretions. Aspirin, ASA; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Modafinil is well distributed in body tissues and is moderately bound to plasma proteins (~60%, mainly to albumin). Concurrent use may decrease atogepant exposure and reduce efficacy. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone. Modafinil is an alerting substance which has been used successfully to treat narcolepsy. Coadministration of pazopanib and modafinil, a CYP3A4 substrate, may cause an increase in systemic concentrations of modafinil. Most rashes have developed within 15 weeks of treatment initiation. Estrogens are metabolized by CYP3A4. 8600 Rockville Pike Sufentanil is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; modafinil is a weak CYP3A inducer. Use of these drugs together can significantly decrease macimorelin plasma concentrations, and may result in a false positive test for growth hormone deficiency. If not possible, monitor doxorubicin closely for efficacy. Cohen S, Ifergane G, Vainer E, Matar MA, Kaplan Z, Zohar J, Math AA, Cohen H. Transl Psychiatry. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. Hydrocodone is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer. These medications include rifabutin. Use caution when concomitant administration of these agents is necessary. Liver metabolism occurs via hydrolytic deamination, S-oxidation, hydroxylation, and glucuronide conjugation. (Moderate) Modafinil is an inducer of CYP3A hepatic enzymes. 200 to 400 mg/day PO has been reported effective. An interaction between modafinil and clozapine has been reported in a case report that resulted in clinical side effects. Conjugated Estrogens; Bazedoxifene: (Moderate) Modafinil is an inducer of CYP3A hepatic enzymes. Modafinil is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Modafinil vs. caffeine: effects on fatigue during sleep deprivation. Lonafarnib is a CYP2C9 substrate and strong CYP3A4 inhibitor; modafinil is a CYP3A4 substrate and CYP2C9 inhibitor. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Cobicistat is an inhibitor/substrate of CYP3A4. Artemether; Lumefantrine: (Major) Modafinil is a substrate/inducer and both components of artemether; lumefantrine are substrates of the CYP3A4 isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations. Remember that this. Simeprevir: (Major) Avoid concurrent use of simeprevir and modafinil. Amprenavir, the active metabolite of fosamprenavir, is a substrate of CYP3A4. Moderate inducers of CYP3A4 can reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin. Theophylline is primarily metabolized by CYP1A2 isoenzymes, with secondary pathways by CYP2E1 and CYP3A4 (minor). Medically Reviewed by James Beckerman, MD, FACC on July 08, 2022 Medications You Should Avoid When You Have Atrial Fibrillation When you have atrial fibrillation (AFib), the medications your doctor. Siponimod: (Moderate) Concomitant use of siponimod and modafinil is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. It is recommended to avoid this combination when codeine is being used for cough. Dosage adjustments may be necessary. The chemical name for modafinil is 2-[(diphenylmethyl)sulfinyl]acetamide. Doravirine: (Moderate) Concurrent administration of doravirine and modafinil may result in decreased doravirine exposure, resulting in potential loss of virologic control. (Major) Coadministration of darunavir with modafinil is not recommended as there is a potential for elevated modafinil concentrations and decreased darunavir concentrations. Modafinil is a moderate CYP3A4 inducer. Rifabutin: (Moderate) Drugs that exhibit significant induction of the hepatic microsomal CYP3A4 isoenzyme may potentially increase the metabolism of modafinil. Modafinil is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone. Drospirenone: (Major) Modafinil may cause failure of oral contraceptives or hormonal contraceptive-containing implants or devices due to induction of CYP3A4 isoenzyme metabolism of the progestins in these products. Linagliptin; Metformin: (Moderate) Concomitant use of linagliptin with modafinil may result in decreased serum concentrations of linagliptin. Tazemetostat is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer. Background Melatonin is a biogenic amine that is found in animals, plants and microbes. Use cannot be routinely recommended. Sharing of CNS stimulant medications can lead to substance abuse disorder and addiction in those they are shared with. (Major) Modafinil may cause failure of oral contraceptives or hormonal contraceptive-containing implants or devices due to induction of CYP3A4 isoenzyme metabolism of the progestins in these products. In addition, ritonavir is a potent CYP3A4 inhibitor. Levamlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Modafinil should be discontinued if rash or other hypersensitivity reaction appears at any time during treatment if an association to the drug is suspected or confirmed. Tolvaptan: (Major) Tolvaptan is metabolized by CYP3A4. Benzphetamine: (Moderate) The use of modafinil with other psychostimulants, including amphetamines (e.g., amphetamine, dextroamphetamine, lisdexamfetamine), has not been extensively studied. Nausea. Coadministration of psychostimulants, such as modafinil, with esketamine may increase blood pressure, including the possibility of hypertensive crisis. Modafinil is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4. Dosage adjustments may be necessary. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating modafinil for excessive sleepiness. If these drugs are used together, monitor patients for a decrease in clinical effects. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response. If these drugs are used together, monitor patients for a decrease in clinical effects. 2007 Jul;65(4):251-7. doi: 10.1016/s0003-4509(07)90043-7. Description and Brand Names. If these drugs are used together, monitor patients for a decrease in clinical effects. Mechanism of Action: The exact mechanism of modafinil's action in reducing somnolence is not fully understood. Dosage adjustments may be necessary. All rights reserved. Venetoclax: (Major) Avoid the concomitant use of venetoclax and modafinil; venetoclax levels may be decreased and its efficacy reduced. If these drugs are used together, monitor patients for a decrease in clinical effects; patients should report breakthrough bleeding to their prescriber. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Dosage adjustments may be necessary. Because the resultant effect of coadministration of a CYP3A4 inducer (modafinil) and inhibitor (ritonavir) on the plasma concentrations of these drugs is not defined, caution and close monitoring are advised if these drugs are administered together. Dosage adjustments may be necessary. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. In addition, modafinil is an inhibitor of the CYP2C19 and CYP2C9 isoenzymes. Use of venetoclax with a moderate CYP3A4 inducer has not been evaluated. Do not keep outdated medicine or medicine no . St. John's Wort, Hypericum perforatum: (Major) St. John's wort, Hypericum Perforatum may reduce the neuronal uptake of monoamines and should be used cautiously with sympathomimetics. Circadian rhythm of rectal temperature during sleep deprivation with modafinil. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. Consideration should be given to increasing the clozapine dose if necessary. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. The probability of effect of apalutamide on modafinil exposure is low due to the existence of multiple pathways for modafinil metabolism, as well as the fact that a non-CYP-related pathway is the most rapid in metabolizing modafinil; however, plasma concentrations of modafinil may be impacted by strong CYP3A4 inducers. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. Zolpidem: (Moderate) It is advisable to closely monitor for reductions in zolpidem efficacy during co-administration of moderate CYP3A4 inducers, such as modafinil. Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Modafinil may cause failure of oral contraceptives or hormonal contraceptive-containing implants or devices due to induction of CYP3A4 isoenzyme metabolism of ethinyl estradiol in these products. Amphetamines: (Moderate) The use of modafinil with other psychostimulants, including amphetamines (e.g., amphetamine, dextroamphetamine, lisdexamfetamine), has not been extensively studied. It is recommended to avoid this combination when hydrocodone is being used for cough. Although this interaction has not been studied, predictions can be made based on metabolic pathways. The molecular formula is C. 15H15NO2S and the molecular weight is 273.35. For geriatric patients, consider lower initial dosage and use careful monitoring. The presence of food delays the rate, but not the extent, of modafinil absorption. In single-dose studies of dextroamphetamine combined with modafinil, no significant pharmacokinetic interactions occurred, but a slight increase in stimulant-associated side effects was noted. Cyclosporine: (Moderate) Modafinil can increase the clearance of cyclosporine by inducing cyclosporine metabolism. Various adverse psychiatric effects have occurred during administration of modafinil including mania, hallucinations, depression, and suicidal ideation. Modafinil is a racemic compound. Concurrent use may increase meloxicam exposure. Caffeine should be avoided or used cautiously with modafinil. Budesonide: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by modafinil may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. Modafinil is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. CYP3A4 is also sensitive to enzyme induction, and a number of drugs are known to be CYP3A4 inducers. Impact of sleep and its disturbances on hypothalamo-pituitary-adrenal axis activity. It is known that many other CNS stimulants may induce severe cardiovascular and cerebrovascular responses if administered in combination with drugs with non-selective MAO inhibitor activity. PDR.net is to be used only as a reference aid. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Experience in a limited number of patients who were greater than 65 years of age in clinical trials showed an incidence of adverse experiences similar to other age groups. Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with modafinil can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. An alternative method or an additional method of contraception should be utilized during modafinil therapy and continued for one month after modafinil discontinuation. An increase in aripiprazole dosage may be clinically warranted in some patients. Caffeine should be used cautiously with modafinil. If modafinil is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Lidocaine is a CYP3A4 and CYP1A2 substrate; modafinil induces both isoenzymes. It is not intended to be a substitute for the exercise of professional judgment. An alternative method or an additional method of contraception should be utilized during modafinil therapy and continued for one month after modafinil discontinuation. The AAP has previously considered amphetamines, when used as drugs of abuse, to be contraindicated in breast-feeding due to concerns of irritability and poor sleeping pattern in the infant. Assess each individual's risk for abuse, misuse, or addiction before prescribing a CNS stimulant, and monitor for the development of these behaviors or conditions throughout treatment. Drospirenone; Estradiol: (Major) Modafinil may cause failure of oral contraceptives or hormonal contraceptive-containing implants or devices due to induction of CYP3A4 isoenzyme metabolism of the progestins in these products. MeSH Simulations suggest that coadministration with a moderate CYP3A4 inducer may decrease ibrutinib exposure by 3-fold. Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of cobicistat with modafinil is not recommended as there is a potential for elevated modafinil concentrations and decreased cobicistat concentrations. An alternative method or an additional method of contraception should be utilized during modafinil therapy and continued for one month after modafinil discontinuation. Lurasidone: (Moderate) Because lurasidone is primarily metabolized by CYP3A4, decreased plasma concentrations of lurasidone may occur when the drug is co-administered with inducers of CYP3A4. Azole antifungals, such as fluconazole, are significant inhibitors of this isoenzyme and may reduce the clearance of modafinil. The most common source of non-medical use is sharing from family or friends with misuse of the patient's own prescription or obtaining from illicit channels occurring less frequently. 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