Modafinilo [Spanish]
Modafinilo [Spanish] - General Information
Modafinilo [Spanish] is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are activated by modafinil. The prexin neuron activation is associated with psychoactivation and euphoria. The exact mechanism of action is unclear, although in vitro studies have shown it to inhibit the reuptake of dopamine by binding to the dopamine reuptake pump, and lead to an increase in extracellular dopamine. Modafinilo [Spanish] activates glutamatergic circuits while inhibiting GABA.
Pharmacology of Modafinilo [Spanish]
Modafinilo [Spanish] is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are activated by modafinil. The prexin neuron activation is associated with psychoactivation and euphoria. Modafinilo [Spanish] is not indicated for complaints of lack of energy or fatigue; but it appears to be very helpful for some patients. Also, it has been used in the treatment of hypersomnia, a disorder in which patients lack the capacity for meaningful sleep and may require ten or more hours per day. Recent studies have have found that modafinil may help recovering cocaine addicts fight their addiction.
Modafinilo [Spanish] for patients
Patient Information:
Modafinil is indicated to treat the sleep disorders, such as, narcolepsy, obstructive sleep apnea/hypopnea
or shift work sleep disorder.
Modafinil may affect the effect of birth control pill. This will last until one
month after stopping Modafinil.
Modafinil may also cause blurred vision, dizziness, changes in thinking and
difficulty controlling movements.
It is recommended that patients who are taking Modafinil, should avoid alcohol.
If you experience the following signs, check with your doctor:
- a strong desire to continue taking the medicine
- a need to increase the dose to receive the same effects
- withdrawal side effects when you stop taking the medicine
- rash or hives
Modafinilo [Spanish] Interactions
CNS Active Drugs
Methylphenidate - In a single-dose study in healthy volunteers, coadministration of modafinil (200 mg) with methylphenidate (40 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with methylphenidate.
Dextroamphetamine - In a single dose study in healthy volunteers, simultaneous administration of modafinil (200 mg) with dextroamphetamine (10 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with dextroamphetamine.
Clomipramine - The coadministration of a single dose of clomipramine (50 mg) on the first of three days of treatment with modafinil (200 mg/day) in healthy volunteers did not show an effect on the pharmacokinetics of either drug. However, one incident of increased levels of clomipramine and its active metabolite desmethylclomipramine has been reported in a patient with narcolepsy during treatment with modafinil.
Triazolam - In the drug interaction study between PROVIGIL and ethinyl estradiol (EE2), on the same days as those for the plasma sampling for EE2 pharmacokinetics, a single dose of triazolam (0.125 mg) was also administered. Mean Cmax and AUC0-∞ of triazolam were decreased by 42% and 59%, respectively, and its elimination half-life was decreased by approximately an hour after the modafinil treatment.
Monoamine Oxidase (MAO) Inhibitors - Interaction studies with monoamine oxidase inhibitors have not been performed. Therefore, caution should be used when concomitantly administering MAO inhibitors and modafinil.
Other Drugs
Warfarin - There were no significant changes in the pharmacokinetic profiles of R- and S- warfarin in healthy subjects given a single dose of racemic warfarin (5 mg) following chronic administration of modafinil (200 mg/day for 7 days) followed by 400 mg/day for 27 days) relative to the profiles in subjects given placebo. However, more frequent monitoring of prothrombin times/INR is advisable whenever PROVIGIL is coadministered with warfarin.
Ethinyl Estradiol - Administration of modafinil to female volunteers once daily at 200 mg/day for 7 days followed by 400 mg/day for 21 days resulted in a mean 11% decrease in Cmax and 18% decrease in AUC0-24 of ethinyl estradiol (EE2; 0.035 mg; administered orally with norgestimate). There was no apparent change in the elimination rate of ethinyl estradiol.
Cyclosporine - One case of an interaction between modafinil and cyclosporine, a substrate of CYP3A4, has been reported in a 41 year old woman who had undergone an organ transplant. After one month of administration of 200 mg/day of modafinil, cyclosporine blood levels were decreased by 50%. The interaction was postulated to be due to the increased metabolism of cyclosporine, since no other factor expected to affect the disposition of the drug had changed. Dosage adjustment for cyclosporine may be needed.
Potential Interactions with Drugs That Inhibit, Induce, or are Metabolized by Cytochrome P-450 Isoenzymes and Other Hepatic Enzymes
In in vitro studies using primary human hepatocyte cultures, modafinil was shown to slightly induce CYP1A2, CYP2B6 and CYP3A4 in a concentration-dependent manner. Although induction results based on in vitro experiments are not necessarily predictive of response in vivo, caution needs to be exercised when PROVIGIL is coadministered with drugs that depend on these three enzymes for their clearance. Specifically, lower blood levels of such drugs could result.
The exposure of human hepatocytes to modafinil in vitro produced an apparent concentration-related suppression of expression of CYP2C9 activity suggesting that there is a potential for a metabolic interaction between modafinil and the substrates of this enzyme (e.g., S-warfarin and phenytoin). In a subsequent clinical study in healthy volunteers, chronic modafinil treatment did not show a significant effect on the single-dose pharmacokinetics of warfarin when compared to placebo.
In vitro studies using human liver microsomes showed that modafinil reversibly inhibited CYP2C19 at pharmacologically relevant concentrations of modafinil. CYP2C19 is also reversibly inhibited, with similar potency, by a circulating metabolite, modafinil sulfone. Although the maximum plasma concentrations of modafinil sulfone are much lower than those of parent modafinil, the combined effect of both compounds could produce sustained partial inhibition of the enzyme. Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, phenytoin (also via CYP2C9) or S-mephenytoin may have prolonged elimination upon coadministration with PROVIGIL and may require dosage reduction and monitoring for toxicity.
Tricyclic antidepressants - CYP2C19 also provides an ancillary pathway for the metabolism of certain tricyclic antidepressants (e.g., clomipramine and desipramine) that are primarily metabolized by CYP2D6. In tricyclic-treated patients deficient in CYP2D6 (i.e., those who are poor metabolizers of debrisoquine; 7-10% of the Caucasian population; similar or lower in other populations), the amount of metabolism by CYP2C19 may be substantially increased. PROVIGIL may cause elevation of the levels of the tricyclics in this subset of patients. Physicians should be aware that a reduction in the dose of tricyclic agents might be needed in these patients.
In addition, due to the partial involvement of CYP3A4 in the metabolic elimination of modafinil, coadministration of potent inducers of CYP3A4 (e.g., carbamazepine, phenobarbital, rifampin) or inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole) could alter the plasma levels of modafinil.
Modafinilo [Spanish] Contraindications
PROVIGIL is contraindicated in patients with known hypersensitivity to modafinil.
Additional information about Modafinilo [Spanish]
Modafinilo [Spanish] Indication: To improve wakefulness in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.
Mechanism Of Action: The exact mechanism of action is unclear, although in vitro studies have shown it to inhibit the reuptake of dopamine by binding to the dopamine reuptake pump, and lead to an increase in extracellular dopamine. Modafinilo [Spanish] activates glutamatergic circuits while inhibiting GABA. Modafinilo [Spanish] is thought to have less potential for abuse than other stimulants due to the absence of any significant euphoric or pleasurable effects. It is possible that modafinil acts by a synergistic combination of mechanisms including direct inhibition of dopamine reuptake, indirect inhibition of noradrenalin reuptake in the VLPO and orexin activation. Modafinilo [Spanish] has partial alpha 1B-adrenergic agonist effects by directly stimulating the receptors.
Drug Interactions: Clozapine Modafinilo [Spanish] increases the effect and toxicity of clozapine
Triazolam Modafinilo [Spanish] decreases the effect of triazolam
Cyclosporine Modafinilo [Spanish] decreases the effect of cyclosporine
Ethinyl Estradiol Modafinilo [Spanish] decreases the effect of the contraceptive
Mestranol Modafinilo [Spanish] decreases the effect of the contraceptive
Food Interactions: Not Available
Generic Name: Modafinil
Synonyms: Not Available
Drug Category: Neuroprotective Agents; Central Nervous System Agents; Anorexigenic Agents; Stimulants
Drug Type: Small Molecule; Approved
Other Brand Names containing Modafinil: Dea No. 1680; Modafinil [Usan-Inn]; Modafinilo [Spanish]; Modafinilum [Latin]; Moderateafinil; Modiodal; Provigil;
Absorption: Rapid following oral administration.
Toxicity (Overdose): Not Available
Protein Binding: 60%
Biotransformation: Hepatic
Half Life: 23-215 hours
Dosage Forms of Modafinilo [Spanish]: Tablet Oral
Chemical IUPAC Name: 2-[di(phenyl)methylsulfinyl]acetamide
Chemical Formula: C15H15NO2S
Modafinil on Wikipedia: https://en.wikipedia.org/wiki/Modafinil
Organisms Affected: Humans and other mammals
