Domina

Composition:

Each tablet contains 150mg Armodafinil.

Pharmacodynamics:

The precise mechanism(s) through which armodafinil (R-enantiomer) or modafinil (mixture of R- and S-enantiomers) promote wakefulness is unknown. Armodafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, both armodafinil and modafinil bind to the dopamine transporter and inhibit dopamine reuptake. Armodafinil and modafinil have wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although their pharmacologic profile is not identical to that of the sympathomimetic amines. In addition to its wake-promoting effects and ability to increase locomotor activity in animals, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants in humans.

Pharmacokinetics:

armodafinil is the longer-lived enantiomer of modafinil and is readily absorbed after oral administration. Peak plasma concentrations are attained at approximately 2 hours in the fasted state. Food effect on the overall bioavailability of armodafinil is considered minimal; however, time to reach peak concentration (tmax) may be delayed by approximately 2-4 hours in the fed state. Since the delay in tmax is also associated with elevated plasma levels later in time, food can potentially affect the onset and time course of pharmacologic action for Armodafinil. Armodafinil is moderately bound to plasma protein (approximately 60%), mainly to albumin. Armodafinil is mainly eliminated via metabolism, predominantly in the liver, with less than 10% of the parent compound excreted in the urine. The apparent terminal t½ is approximately 15 hours.

Indications:

Armogil is indicated to improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy and shift work disorders.

In OSA Armogil is indicated as an adjunct to standard treatment(s) for the underlying obstruction. 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 NODEMENT for excessive sleepiness.

Contraindications:

Armodafinil is contraindicated in patients with known hypersensitivity to modafinil and armodafinil or its inactive ingredients.

Dosage and Administration:

Obstructive Sleep Apnea (OSA) and Narcolepsy:

The recommended dose of Armogil for patients with OSA or narcolepsy is 150 mg or 250 mg given as a single dose in the morning. In patients with OSA, doses up to 250 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 150 mg/day dose.

Shift Work Disorder (SWD):

The recommended dose of Armogil for patients with SWD is 150 mg given daily approximately 1 hour prior to the start of their work shift.

Dosage Modification in Patients with Severe Hepatic Impairment:

In patients with severe hepatic impairment, the dosage of Armogil should be reduced.

Use In Geriatric Patients:

Consideration should be given to the use of lower doses and close monitoring in geriatric patients.

Warnings and Precautions:

serious rash requiring hospitalization and discontinuation of treatment has been reported in adults in association with the use of modafinil and armodafinil and in children in association with the use of modafinil. Armodafinil has not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication.
Case of possible Stevens-Johnson syndrome (SJS) and 1 case of apparent multi-organ hypersensitivity reaction/ Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). Several of the cases were associated with fever and other abnormalities (e.g., vomiting, leukopenia).

·(DRESS)/Multiorgan Hypersensitivity: DRESS, also known as multi-organ hypersensitivity, has been reported with Armodafinil. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. One fatal case of DRESS that occurred in close temporal association (3 weeks) with the initiation of Armodafinil treatment has been reported in the post marketing setting.

·Angioedema And Anaphylaxis Reactions: Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm), were observed. Patients should be advised to discontinue therapy and immediately report to their physician any signs or symptoms suggesting angioedema or anaphylaxis (e.g., swelling of face, eyes, lips, tongue or larynx; difficulty in swallowing or breathing; hoarseness).

·Persistent Sleepiness: Patients with abnormal levels of sleepiness who take Armodafinil should be advised that their level of wakefulness may not return to normal. Patients with excessive sleepiness, including those taking Armodafinil, should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity. Prescribers should also be aware that patients may not acknowledge sleepiness or drowsiness until directly questioned about drowsiness or sleepiness during specific activities.

·Psychiatric Symptoms: anxiety, agitation, nervousness, and irritability were reasons for treatment discontinuation more often in patients on Armodafinil compared to placebo. Depression was also a reason for treatment discontinuation more often in patients on Armodafinil compared to placebo. Cases of suicidal ideation were observed in clinical trials.

·Caution should be exercised when Armodafinil is given to patients with a history of psychosis, depression, or mania.

·Effects on ability to drive and use machinery: Although Armodafinil has not been shown to produce functional impairment, any drug affecting the central nervous system (CNS) may alter judgment, thinking or motor skills. Patients should be cautioned about operating an automobile or other hazardous machinery until it is reasonably certain that Armodafinil therapy will not adversely affect their ability to engage in such activities.

·Cardiovascular Events: In clinical studies of Armodafinil, cardiovascular adverse reactions, including chest pain, palpitations, dyspnea and transient ischemic T-wave changes on ECG were observed in three subjects in association with mitral valve prolapse or left ventricular hypertrophy. It is recommended that Armodafinil tablets not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced the mitral valve prolapse syndrome when previously receiving CNS stimulants.

·Wakefulness: Advise patients that treatment with Armodafinil will not eliminate their abnormal tendency to fall asleep. Advise patients that they should not alter their previous behavior with regard to potentially dangerous activities (e.g., driving, operating machinery) or other activities requiring appropriate levels of wakefulness, until and unless treatment with Armodafinil has been shown to produce levels of wakefulness that permit such activities. Advise patients that Armodafinil is not a replacement for sleep.

Continuing Previously Prescribed Treatments:

Inform patients that it may be critical that they continue to take their previously prescribed treatments (e.g., patients with OSA receiving CPAP should continue to do so).

Side Effects:

Most common: headache, nausea, dizziness, and insomnia.

Common: palpitations, diarrhea, dry mouth, dyspepsia, abdominal pain, constipations, vomiting, loose stools, fatigue, thirst, influenza-like illness, pyrexia, seasonal allergy, increased heart rate, anorexia, increased appetite, headache, dizziness, disturbance in attention, tremor, migraine, paresthesia, anxiety, depression, agitation, nervousness, depressed mood, polyuria, dyspnea, rash, contact dermatitis, hyperhidrosis, and an increase in Gamma-Glutamyl transferase.

Drug Interactions:

Effects of Armodafinil on CYP3A4/5 Substrates:

The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by Armodafinil via induction of metabolic enzymes, which results in lower systemic exposure. Dosage adjustment of these drugs should be considered when these drugs are used concomitantly with Armodafinil.

The effectiveness of steroidal contraceptives may be reduced when used with Armodafinil and for one month after discontinuation of therapy. Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives (e.g., ethinyl estradiol) when treated concomitantly with Armodafinil and for one month after discontinuation of Armodafinil treatment.

Blood levels of cyclosporine may be reduced when used with Armodafinil. Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when used concomitantly with Armodafinil.

Effects of Armodafinil on CYP2C19 Substrates:

Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by Armodafinil via inhibition of metabolic enzymes, with resultant higher systemic exposure. Dose reduction of these drugs may be required when these drugs are used concomitantly with Armodafinil.

Warfarin:

More frequent monitoring of prothrombin times/INR should be considered whenever Armodafinil is co-administered with warfarin

Monoamine Oxidase (MAO) Inhibitors:

Caution should be used when concomitantly administering MAO inhibitors and Armodafinil.

Pregnancy:

Category C. There are no adequate and well-controlled studies of either armodafinil or modafinil in pregnant women. Two cases of intrauterine growth retardation and one case of spontaneous abortion have been reported in association with armodafinil and modafinil. Armodafinil or modafinil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers:

It is not known whether armodafinil or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when armodafinil tablets are administered to a nursing woman.

Overdosage:

Fatal overdoses involving modafinil alone or involving Armodafinil or modafinil in combination with other drugs have been reported in the post marketing setting. Symptoms most often accompanying Armodafinil or modafinil overdose, alone or in combination with other drugs, have included anxiety, dyspnea, insomnia; central nervous system symptoms such as restlessness, disorientation, confusion, excitation and hallucination; digestive changes such as nausea and diarrhea; and cardiovascular changes such as tachycardia, bradycardia, hypertension, and chest pain.

No specific antidote exists for the toxic effects of armodafinil overdose. Such overdoses should be managed with primarily supportive care, including cardiovascular monitoring.

Drug Abuse and Dependence:

Abuse of Armodafinil has been reported in patients treated with Armodafinil. Patterns of abuse have included euphoric mood and use of increasingly large doses or recurrent use of Armodafinil for a desired effect.

Abuse of armodafinil, poses a risk of overdosage similar to that seen for modafinil, which may lead to tachycardia, insomnia, agitation, dizziness, anxiety, nausea, headache, dystonia, tremor, chest pain, hypertension, seizures, delirium, or hallucinations. Other signs and symptoms of CNS stimulant abuse include tachypnea, sweating, dilated pupils, hyperactivity, restlessness, decreased appetite, loss of coordination, flushed skin, vomiting, and abdominal pain.

In humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking and feelings, typical of other CNS stimulants.

Physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. Patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior).

Physical dependence can occur in patients treated with Armodafinil. Abrupt cessation or dose reduction following chronic use can result in withdrawal symptoms, including shaking, sweating, chills, nausea, vomiting, confusion, aggression, and atrial fibrillation.

Drug withdrawal convulsions, suicidality, fatigue, insomnia, aches, depression and headache have also been observed during the post marketing period. Also, abrupt withdrawal has caused deterioration of psychiatric symptoms such as depression.