CNS Stimulants - Analeptics include-

   Caffeine citrate, Doxapram Hcl, Modanafinil, Armodafinil

Drug interactions- summary

CYP3A4 inducers eg. itraconazole, Ketoconazole   + Mazepine, Phenobarbital  +  Modafinil 
 CYP3A4 could alter the plasma levels of modafinil                                          
                                                                                       
MAOIs eg. phenelzine   + Modafinil
Use caution when administering MAOIs and modafinil           
                                                                                                    
 Methylphenidate,  Dextroamphetamine    +  Modafinil
 Modfinil absorption may be delayed by approx    1  hour   
                                                                                             
Modafinil  + Alcohol  
Avoid coadministration   
                                                                                   
Modafinil  + Clozapine
Clozapine serum levels increasing the  pharmacologic and toxic effects
                                                                                      
Modafinil  + Contraceptives hormonal estrogens
Effectiveness of hormonal  contraceptives  and estrogens may be reduced.
 Use  alernative methods

Modafinil   + Cyclosporine 
Cyclosporine blood levels decreased.  Cyclosporine dosage adjustment needed                                                                                         
 -                                                                                            
Modafinil  +    CYP2C9 /2C19  eg. Diazepam, Propranol, Certain Antidepress, eg. Clomipramine,
 Desipramine
Coadmin. with modafinil  may require dosage reduction and reduction and monitor for toxicity                                                    
                                    
                                 
Modafinil  +   CYP1A2, CYP2B6, CYP3A4  substrates
Use caution   when modafinil is coadmin,                                                                          
                                                                                 
Modafinil    +    Triazolam
Triazolam Cmax AUC and half life decreased

Sleep disorder - to improve wakefulness in patients

 CNS Stimulants - Analeptics include-

Caffeine citrate, Doxapram Hcl, Modafinil, Armodafinil

INFORMATION UPDATE-

SERIOUS SKIN AND PSYCHIATRIC ADVERSE DRUG REACTIONS-

There have been reports of Stevens- Johnson Syndrome erythema multiforme and toxic
epidermal necrolysis with the use modanafil (sold as MODAPRO etc. Hence-

Treatment  should be discontinued at the first sign of rash and not restarted .
Suicide ideation, hallucinations, delusions, aggression, psychosis, and mania
have been reported .

Treatment should be discontinued in patients who experience any psychiatric symptoms
and should not be restarted

Modanafinil shoould be used with caution in patients with a history of psychosis, depression,
or mania and patients with a history of alcohol, or illicit substance abuse. ( MIMS )

 Adverse reactions- 
                                           
MODANAFIL -
------------------

CARDIOVASCULAR - 

 Hypertension 3%  Palpitation  2%  Tachycardia  2%  Vasodilation   2%   

CNS-

 Headache  34% Nervousness 7%     Anxiety 5%  Dizziness 5%  Insomnia 5%
 Depression 2%  Agitation 1%  Confusion 1% 

DERMATOLOGIC -

Herpes simplex   1%  Sweating 1%

GI-   

  Nausea  11% Diarrhea  6% Dyspepsia  5%  Anorexia 4%  Dry mouth  4% 
   Flatulance, Mouth ulceration, Thirst 1% 

GU-   

  Hematuria, Pyuria, Urine abnormality 1%

HEMATOLOGICAL /LYMPHATIC - 

Eosinophilia 1%   

RESPIRATORY - 

 Rhinitis  7%    Pharyngitis 4% Lung disorder  2%  Asthma, Epistaxis 1%

SPECIAL SENSES -

 Abnormal vision , Amblyopia, Eye pain 1%

MISCELLANEOUS -     

 Back pain 6%, Flu syndrome 4% Chest pain  3% Chills, Neck rigidity 1%

Known hypersensitivity to modafinil, armodafinal ot its ingredients

Warnings /precautions-

Dermatologic- serious rash requiring hospitization and discontinuation of treatment has been reported in adults and children in association with the use of modafinil

Persistent sleepiness- advise patients with abnormal levels of sleepness who take modfinil that their level of wakefulness may not return to normal

Psychiatric effects- There have been reports of adverse experiences in patients treated with modifinil

Cardiovascular effects- in clinical studies of modafinil, signs and symptoms, including ,chest pain, palpitations, dyspnea, and transcient T -wave changes in ECG were observed.

Abuse potential and dependence- observe patients for signs of misuse or abuse - drug seeking behaviour

Hazardous tasks- caution patients about operating hazardous machinery or automobile until they are reasonably certain that modfinil will not adversely affect their ability to engage in such activities

Pregnancy- use modanifil during pregnancy only if the potential benefit justifies the potential risk to the fetus

Labor and delivery- the effect of modafinil on labor and delivery in humans has not been systematically investigated

Lactation- excercise caution when modafinil is admninistered to breast feeding woman.

Indication-

Sleep disorder - to improve wakefulness in patients

Dosage-

200-400mg daily in 2 divided doses in the morning and after noon. or a single dose in the morning

Elderly- initially 100mg daily maximum 400mg daily in absence of hepatic impairment

Nnot recommended for patients below 16 years

CNS Stimulants - Analeptics include-

Caffeine citrate, Doxapram Hcl, Modanafinil, Armodafinil

1. Modafinil is indicated for patients who have abnormal levels of sleepiness. Modfinil has been shown to improve but not eliminate this abnormal tendency to this abnormal tendenct to fall asleep

2. Therefore, patients should alter their previous behaviour with regards to potentially dangerous activites requiring appropiate levels of wakefulness , until treatment with modfinil has shown to produce levels of wakefulness that permits such activites

3. Advice patients to contact their health care provider if they experience anxiety, chest pain, depression, rash, or sign of psychosis or mania

4. Advice patient to stop taking modafinil and to notify their doctor if they develop blisters, hives, mouth sores, peeling skin, rash, trouble swallowing or breathing or a related allergic phenomenon

5. Advice patients to notify their physician if they are pregnant , intend to become pregnant during therapy or are breast feeding an infant

6. Caution patients regarding the potentially increased risk f pregnancy when using steroid contraceptives with modfinil and for 1 month after discontinuation of therapy

7. Advice patients that the use of modafinil in combination has not been studied.

Advice patients that it is prudent to avoid alcohol while taking modafinil

CNS Stimulant Analeleptics

Pharmacology-

The precise mechanism throug which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions like sympathomimetics agents, including amphetamine and methylphenidate although the pharmacologic profile is not identical to that sympathomimetic amines

Pharmacology-

Modafinil is a racemic compd whose enantiomers have different pharmacokinetics eg. the half life of L-isomer is approx, 3 times that of the d-isomer

The absorption of modafinil is rapid and peak conc. occurs at 2-4 hours. The effective elimination half-life after multiple doses is about 15 hours. The major route of elimination ( approx. 90% ) is metabolism, primarily by the liver

Food has no effect on overall modofinil bioavailability

Pregnancy-

Use modanifil during pregnancy only if the potential benefit justifies the potential risk to the fetus

Labor and delivery-

The effect of modafinil on labor and delivery in humans has not been systematically investigated

Lactation-

Excercise caution when modafinil is admninistered to breast feeding woman.