Provigil drug decsription

Description

Provigil is a brand that is registered to sell a wakefulness-inducing substance Modafinil. The pills comprise 100 or 200 mg of Modafinil, a substance of white color. Besides it, the tablets also contain components such as starch, lactose, and others.

Directions for therapy with Provigil

The formulation is above all indicated for the managing of excessive sluggishness in persons with narcolepsy. Besides, it is authorized for sleepiness management in such diagnoses as obstructive sleep apnea (OSA), or shift work disorder (SWSD). The medication does not provide a therapeutic action for the cause of OSA, it only helps to cope with the daytime loss of productivity due to bad sleep at night but other therapeutic measures should be undertaken to eliminate the symptoms of the condition.

Dosages of Provigil

Narcolepsy and OSA

The regular dose is 100 or 200 mg taken before noon.

If the dosage is insufficient, it can be doubled and also taken before noon. There is no data on the better efficacy of the higher dosages.

SWSD therapy

Adverse effects statistics during clinical tests Clinical tests of medications are made under certain conditions and with a restricted number of participants so their results cannot be directly compared to the rate of such reactions occurrence in individuals who use the drug outside the trial. The medication had been tested for effectiveness and harmlessness in over 3000 persons with 2000 of them being diagnosed with narcolepsy, SWSD, and OSA. According to the tests in which one group of patients was given placebo and another Provigil, the most usual side effect was headache, mild nausea, irritability, nasal congestion or such burping nausea, and others. Negative effects developed in more than 1% of volunteers and reported more frequently by the testers of Modafinil than placebo. The regular dose for SWSD is also 100-200 mg but it is taken before the shift start.

Provigil dosage adjustments in liver/kidney diseases

- The dosages for individuals with mild to moderate kidney dysfunction remain unchanged. In severe kidney failure, the dosages should be chosen by a doctor.

- In severe liver function failure, the dose is cut in two.

Available forms

The medication is available in two strengths per pill – 100 mg and 200 mg.

Storage conditions

Store the pills in their original package at the temperature from 20-25C (68-77F) in normal humidity.

Provigil adverse reactions

The serious negative reactions that can be developed due to the formulation use include:

- Allergic skin rash;

- Allergic swelling and anaphylactic reactions;

- Persistent insomnia;

- Mental disorders or aggravation of existing ones;

- Heart function disorders.

Adverse effects statistics during clinical tests

Clinical tests of medications are made under certain conditions and with a restricted number of participants so their results cannot be directly compared to the rate of such reactions occurrence in individuals who use the drug outside the trial.

The medication had been tested for effectiveness and harmlessness in over 3000 persons with 2000 of them being diagnosed with narcolepsy, SWSD, and OSA.

According to the tests in which one group of patients was given placebo and another Provigil, the most usual side effect was headache, mild nausea, irritability, nasal congestion or such burping nausea, and others.

Negative effects developed in more than 1% of volunteers and reported more frequently by the testers of Modafinil than placebo.

The trial included using different dosages: from 100 mg to 400 mg a day. With the rise of the dosages, headache, and nausea developed in more individuals.

These were also the reasons for the formulation use discontinuation that made total of 8% of volunteers who participated in the trials in comparison with 3% who quit the therapy due to negative effects while receiving a placebo.

Influence of Provigil on laboratory indicators

The tests included blood composition changes and urine composition analysis. The use of Provigil is noted to be related to insignificant changes in normal parameters. It doesn’t provide any effect on the liver enzymes concentrations.

Modafinil interactions

- The formulation enhances the action of the liver enzyme CYP3A4 which participates in the washing out from the body of some medications such as hormonal birth control, cyclosporine, midazolam, and others which results in their lowered effect. Thus, in concurrent use with the stimulant, their dosages must be revised and in case of contraceptives use, it is advised to opt for barrier contraception.

- Provigil also affects the washing out of substances metabolized with the participation of CYP2C19 enzyme including diazepam, Omeprazole, and others. These formulations are longer washed out from the body than normally when combined with Modafinil. It is encouraged to revise the dosages of such medications when they are co-administered with Provigil.

- It is not advised to combine Modafinil with any MAO inhibitors as it can result in severe adverse effects.

- If a patient uses Warfarin along with Provigil, prothrombin time should be measured more often than usually.

Abuse and addiction development potential

The active agent of Provigil, Modafinil, provides CNS stimulating effects, improves mood, perception, and so on. This action is due to the inhibition of dopamine recapture but the medication doesn’t cause enhanced dopamine production in the body. But due to its effects, it is should not be prescribed for people with a history of substance abuse or they must be closely monitored while undergoing the therapy with the drug. As for physiological addiction, during the 9-week studies and the following withdrawal of the formulation, no patients showed signs of withdrawal.

WARNINGS

- The medication is able to cause severe skin rash. In case of its occurrence, Provigil use must be discontinued and medical assistance sought.

- The formulation is not authorized for use in kids as it is more likely to cause severe allergic reactions in them. The rate of skin rash and other allergic manifestations in patients younger than 17 years that led to the cessation of the therapy was 0.8%. The average time for skin reactions development was two weeks. In post clinical trial period, there had been several cases of severe allergic reactions that make the incidence of 1 to 2 cases per one million Provigil users.

Other life-threatening allergic reactions (swelling and anaphylaxis)

In the course of clinical trials, no cases of allergic edema or anaphylaxis were recorded. However, during the trials of the slightly changed formula known as Armodafinil, one in 1600 patients showed signs of skin rash and suffocation which are considered a part of anaphylaxis reaction. Due to this, it is advised for all individuals who use Provigil discontinue the use of the formulation in any signs of trouble breathing, skin rash, or puffiness of the face, lips, etc.

Mental dysfunctions

Mental condition signs are more likely to be developed in individuals who have a history of mental dysfunctions and take Modafinil. The reported symptoms included manic episodes, hallucinations, aggression, anxiety, and others. The total number of individuals who reported discontinuing the formulation use to such effects is less than 1%.

Safety recommendations

- The medications based on Modafinil should be taken only by people with diagnosed conditions associated with extreme daytime sleepiness. For the correct diagnosis, physiological examination, patient questioning, and sleep tests are made.

- There are no data on the negative effect of Modafinil on time or reaction and other thinking or motor skills but it is still advised to render caution driving vehicles or operating any machinery during the first weeks of the medication use as it is a substance that affects the CNS and can cause dangerous adverse effects.

- For patients with OSA, the main treatment must be implemented for the removal of airways obstruction and Provigil used as an additional therapy to cope with sleepiness.

- The safety of Modafinil in individuals with recent acute heart conditions such as heart attack isn’t studied. Considering that the medication can cause chest pain, irregular heartbeat and other negative heart function symptoms, it is advised not to prescribe it for individuals with heart problems.

- The medication doesn’t provoke any significant blood tension raise in individuals without hypertension but individuals with hypertension may need dosage raise of their blood pressure medications.

- Hormonal means of contraception show lower efficacy when used along with Provigil so other additional means of contraception must be utilized. - Modafinil can lower the action of cyclosporine so if the medicines are used concurrently, their dose should be increased.

- Individuals with severe liver failure should receive lower dosages of Modafinil.

- There is no data on the formulation use in individuals with severe kidney failure.

Carcinogenicity, potential to cause mutations, impact on childbirth

- The tests of the formulation on animals had shown that it doesn’t have the potential to cause cancer. During the studies, significantly raised dosages of Modafinil had been tested.

- The tests of the formulation on animals had shown that it doesn’t have the potential to cause cells mutation.

- The tests of the formulation on animals had shown that it doesn’t have the potential to cause fertility problems. In the course of the studies, significantly elevated dosages of Modafinil had been tested.

- Modafinil is classified pregnancy category C (contraindicated) because during the tests on animals, it shown toxicity for fetus.

Provigil overdose study

- The tests on the effect of high doses of Modafinil on human body included the administration of 1000-1600 mg of the substance per day to volunteers for one to three weeks. The results have shown no health damage and any life-threatening effects. The usual symptoms included excitation, trouble falling asleep, restlessness, and others.

- In total, since the formulation is on the market, several cases of fatal overdose when the medication was combined with other potent drugs have been reported.

- Accidental intake of the formulation in high doses in children recorded in children hadn’t led to any dangerous side effects besides insomnia, agitation, restlessness, etc.

- There is no antidote for the formulation so in case of excessive dose intake and occurrence of pronounced adverse reactions symptomatic measures are needed. - Provigil contraindications for use

- The medication is contraindicated for individuals with an allergy to the active ingredients of Provigil.

How does Modafinil work?

The exact principles of the formulation action that render wakefulness enhancement are not fully understood. It is considered that it has an effect compared to that of sympathomimetic substances such as amphetamine. The medication has a mild effect on dopamine preventing its recapture and thus increasing its levels in the brain without promoting its initial release.

During the tests on animals, the significantly elevated activity in some areas of the brain was observed which caused enhanced motor activity but there is no evidence that it has the same effects in human.

Besides the wakefulness-enhancing effects, it is also noted that Modafinil induces mild euphoria, improvement of mood, perception, thinking, and feelings which is a common feature of other nervous system stimulants.

Absorption of Provigil

The formulation is quickly absorbed from the digestive tract in the blood with the top concentration achieved in two to four hour after a pill intake. The absorption isn’t influenced by food but it can slightly delay the time of highest concentration achieved.

Metabolism of Provigil

90% of the formulation is metabolized in the liver and washed out in the urine.

Efficacy of Provigil for different conditions

Narcolepsy

The initial tests of the formulation effectiveness in narcolepsy have been held in the US and included nine-week trials with the participation of 560 patients with complaints of excess daily sleepiness and the proven diagnosis through sleep tests, medical surveys, etc. The trials included giving random patients placebo and others - Provigil. It was a double-blind study that helped to discover the effectiveness of Modafinil-based medication without biased opinions.

The tools for the formulation effectiveness assessment included sleep latency tests, wakefulness test, and patient’s survey on their personal assessment of their condition. Based on them, the formulation administered in the dosage between 200 and 400 mg provides a substantial improvement of wakefulness based both on subjective and objective criteria.

OSA

In the tests of the formulation efficacy for persons with OSA participated 327 patients from who were randomly chosen people who were administered placebo and those who got Provigil for the course of three months. The study included only the individuals with confirmed OSA based on patients’ survey, sleep tests, tests of breathing interruptions during sleep for at least ten seconds, and other approved criterions. The individuals who were administered Provigil were given dosages of 200 or 400 mg a day.

Based on the subjective and objective data collected, individuals who received the formulation showed a substantial improve of subjective and objectively measured wakefulness.

Shift-work sleep disorder

The efficacy of the formulation in patients with SWSD was tested during the clinical trials that lasted three months and comprised in total 210 patients with a diagnostically proven disorder based on the objective measures (proven sleep desynchronization via sleep tests) and complaints of the patients. The patients were chosen also based on the criterion that they suffered from insomnia and violated the sleep-wake cycle for not less than three months in a row.

The results had shown that people who received Provigil rather than placebo had enjoyed improved daytime wakefulness and substantial time extension they fall asleep during the day.