Posted by michael on June 10, 2000, at 17:35:50
In reply to More:Provigil poop out;klono counteracts provigil?, posted by Rick on June 10, 2000, at 16:32:05
(It would be interesting to see a French monograph for Provigil.)
>
The french one's difficult to read - this one is from a brittish db. It appears they've been using it at least since 1997, possibly longer...Cephalon UK Limited
11/13 Frederick Sanger Road
Surrey Research Park
Guildford GU2 5YD
Telephone: 01483 453360 Facsimile: 01483 453324
PROVIGIL TM
Qualitative and quantitative composition
Modafinil 100 mg per tablet.Pharmaceutical form
Tablets.Clinical particulars
Therapeutic indications: Narcolepsy.
Posology and Method of Administration:Adults: The recommended daily dose is 200-400 mg. PROVIGIL may be taken as two divided doses in the morning and at noon, or as a single dose in the morning according to physician assessment of the patient and the patient's response.
Elderly: There are limited data available on the use of PROVIGIL in elderly patients. In view of lower clearance and increased AUC, it is recommended that patients over 65 years of age should commence therapy at 100 mg daily. The maximum dose of 400 mg per day should only be used in the absence of renal or hepatic impairment.
Hepatic and renal failure: The dose in patients with severe hepatic or renal failure should be reduced by half (100-200 mg/day).
Children: See Contra-indications.
Contra-indications: PROVIGIL is contra-indicated for use during pregnancy and lactation, in children, moderate to severe hypertension, and arrhythmia. Known hypersensitivity to PROVIGIL or any component of the preparation.
Special warnings and special precautions for use: Patients with major anxiety should only receive treatment with PROVIGIL in a specialist unit.
Sexually active women of child-bearing potential should be established on a contraceptive programme before taking PROVIGIL.
Blood pressure and heart rate should be monitored in hypertensive patients.
It is recommended that PROVIGIL tablets not be used in patients with a history of left ventricular hypertrophy or ischaemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with CNS stimulant use.
Whilst studies with modafinil have demonstrated a low potential for dependence, as with other psychoactive agents, the possibility of dependence with long term use cannot be entirely excluded.
Interactions with other medicaments and other forms of interaction:
Oral contraceptives: The effectiveness of oral contraceptives may be impaired due to enzyme induction activity of PROVIGIL. When oral contraceptives are used, a product containing 50 micrograms or more of ethinyl oestradiol should be taken. Adequate contraception will require continuation of the oral contraceptive for two cycles after stopping PROVIGIL.
Tricyclic antidepressants: In a single dose pharmacokinetic interaction study of PROVIGIL (200 mg) and clomipramine (50 mg), no clinically important alterations in the pharmacokinetic profile of PROVIGIL or clomipramine were noted, however, patients receiving such medication should be carefully monitored.
Anti-convulsant therapy: In view of the enzyme inducing potential of PROVIGIL, care should be observed with co-administration of these drugs.
Pregnancy and lactation: Modafinil has been shown to be non-teratogenic in preclinical reproductive toxicology investigations at doses greater than the maximum clinical dose. However, blood levels in preclinical safety studies, due to metabolic autoinduction, were less than or similar to that expected in patients. As there have been no adequate or well controlled studies of modafinil in pregnant women, PROVIGIL should be contra-indicated for use in pregnancy and lactation.
Effects on ability to drive and use machines: There is no information available concerning the effects of PROVIGIL on vehicle driving and/or the ability to use machinery.
Undesirable effects: Episodes of feelings of nervousness, excitation, aggressive tendencies, insomnia, personality disorder, anorexia, headache, CNS stimulation, euphoria, abdominal pain, dry mouth, palpitation, tachycardia, hypertension, and tremor have been reported.
Gastrointestinal disturbances (nausea, gastric discomfort) have been reported in clinical trials, usually regressing when tablets are taken during meals. There have also been reports of pruritic skin rashes and, very rarely, cases of buccofacial dyskinesia.
A dose related increase in alkaline phosphatase has been observed.
The safety of PROVIGIL has not been studied beyond 40 weeks of continuous use.
Overdose: The chief symptom following massive ingestion is insomnia.
Management: Induced emesis or gastric lavage should be considered. Hospitalisation and surveillance of psychomotor status; cardiovascular monitoring or surveillance until the patient's symptoms have resolved.
Pharmacological properties
Pharmacodynamic properties: Modafinil promotes wakefulness in a variety of species, including man. The precise mechanism(s) through which modafinil promotes wakefulness is unknown, although the wake-promoting effects of modafinil can be attenuated by alpha-adrenergic antagonists.
Modafinil in man restores and/or improves the level of wakefulness and daytime alertness in relation to the dose administered. Starting from the dose of 100 mg in the morning, changes are found in electrophysiological parameters reflecting alertness (ratio of power of alpha rhythm to power of ;gq rhythm). Starting from 200 mg in the morning, an increase is seen in latency periods in the multiple sleep latency test. It opposes the impairment of cognitive (memory in particular), psychomotor and neurosensorial performances induced by sleep deprivation. This activity is obtained in the absence of any modifications concerning behaviour, appetite and habituation.Morning administration of 200 mg does not appear to affect nocturnal sleep. Administration of 100 mg morning and noon may prolong the subjective time taken to fall asleep. Evening administration may disturb sleep. This pharmacodynamic activity does not appear to affect the autonomic nervous system.
Pharmacokinetic properties: The pharmacokinetics of modafinil are linear and independent of the dose administered. Absorption of modafinil following oral administration is good but slow. Peak plasma concentration is reached two to three hours after ingestion. Amounts absorbed increase in proportion to doses administered.
Modafinil is moderately bound to plasma proteins (62%), essentially to albumin. This degree of protein binding is such that the risk of interaction with strongly bound drugs is unlikely.
Modafinil is metabolised by the liver. The chief metabolite (40-50% of the dose), acid modafinil, has no pharmacological activity. The excretion of modafinil and its metabolites is chiefly renal, with a small proportion being eliminated unchanged (< 10%).
The elimination half-life of modafinil is long (10-12 hours) and enables a treatment regimen based upon one or two doses/day.
Preclinical safety data: Toxicology studies by single and repeated dosing have revealed no particular toxic action in animals.
Reproduction function studies have revealed no effect on fertility, nor any teratogenic effect, nor any effect on viability, growth or development of the offspring.
This drug is not considered to be mutagenic or carcinogenic.
Animal exposure to modafinil, based on actual blood levels in the general toxicology, reproductive and carcinogenicity studies, was less than or similar to that expected in humans. This circumstance is the result of metabolic auto-induction noted in the preclinical studies. However, animal exposure on a mg/kg dose basis to modafinil in the general toxicology, reproductive and carcinogenicity studies was greater than the expected exposure, calculated on a similar basis, in humans.
Pharmaceutical particulars
List of excipients: Lactose monohydrate, corn starch, magnesium silicate, croscarmellose sodium, povidone K90, talc and magnesium stearate.
Incompatibilities: None knownShelf life: Three years
Special precautions for storage: Store at less than 25°C in a dry place. Protect from direct heat and sunlight.
Nature and contents of container: 30 tablets in PVC/PE/Aclar/Aluminium blister
60 tablets in PVC/PE/Aclar/Aluminium blister
90 tablets in PVC/PE/Aclar/Aluminium blister
Instructions for use/handling: Not applicable.
Marketing authorisation number
PL 16260/0001Date of first authorisation/renewal of authorisation
14 October 1997Date of (partial) revision of text
22 June 1998
poster:michael
thread:36517
URL: http://www.dr-bob.org/babble/20000610/msgs/36869.html