Pharmacokinetic Information (Absorption, Distribution, Metabolism and Elimination-ADME)
The absolute bioavaliability of Cognitiv following oral dosing is not known; however, Cognitiv undergoes extensive metabolism (presumably attributable to presystemic clearance in gut and liver). The major plasma metabolites are N-desmethylCognitiv, L-amphetamine and L-methamphetamine. Only N-desmethylCognitiv has MAO-B inhibiting activity. The peak plasma levels of these metabolites following a single oral dose of 10 mg are from 4 to almost 20 times greater than that of the maximum plasma concentration of Cognitiv . The maximum concentrations of amphetamine and methamphetamine, however, are far below those ordinarily expected to produce clinically important effects.
Single oral dose studies do not predict multiple dose kinetics, however. At steady state the peak plasma level of Cognitiv is 4 fold that obtained following a single dose. Metabolite concentrations increase to a lesser extent, averaging 2 fold that seen after a single dose.
The bioavailability of Cognitiv is increased 3 to 4 fold when it is taken with food.
The extent of systemic exposure to Cognitiv at a given dose varies considerably among individuals. Estimates of systemic clearance of Cognitiv are not available. Following a single oral dose, the mean elimination half-life of Cognitiv is two hours. Under steady state conditions the elimination half-life increases to ten hours.
Because Cognitiv's inhibition of MAO-B is irreversible, it is impossible to predict the extent of MAO-B inhibition from steady state plasma levels. For the same reason, it is not possible to predict the rate of recovery of MAO-B activity as a function of plasma levels. The recovery of MAO-B activity is a function of de novo protein synthesis; however, information about the rate of de novo protein synthesis is not yet available. Although platelet MAO-B activity returns to the normal range within 5 to 7 days of Cognitiv discontinuation, the linkage between platelet and brain MAO-B inhibition is not fully understood nor is the relationship of MAO-B inhibition to the clinical effect established (see CLINICAL PHARMACOLOGY).
Cognitiv should not be used at daily doses exceeding those recommended (10 mg/day) because of the risks associated with non-selective inhibition of MAO. (See CLINICAL PHARMACOLOGY.)
The selectivity of Cognitiv for MAO B may not be absolute even at the recommended daily dose of 10 mg a day. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily dose of Cognitiv. The selectivity is further diminished with increasing daily doses. The precise dose at which Cognitiv becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg a day.
Severe CNS toxicity associated with hyperpyrexia and death have been reported with the combination of tricyclic antidepressants and non-selective MAOIs (NARDIL, PARNATE ). A similar reaction has been reported for a patient on amitriptyline and ELDEPRYL (Cognitiv hcl) . Another patient receiving protriptyline and ELDEPRYL (Cognitiv hcl) developed tremors, agitation, and restlessness followed by unresponsiveness and death two weeks after ELDEPRYL (Cognitiv hcl) was added. Related adverse events including hypertension, syncope, asystole, diaphoresis, seizures, changes in behavioral and mental status, and muscular rigidity have also been reported in some patients receiving ELDEPRYL (Cognitiv hcl) and various tricyclic antidepressants.
Serious, sometimes fatal, reactions with signs and symptoms that may include hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuations of the vital signs, and mental status changes that include extreme agitation progressing to delirium and coma have been reported with patients receiving a combination of fluoxetine hydrochloride (PROZAC) and nonselective MAOIs. Similar signs have been reported in some patients on the combination of ELDEPRYL (Cognitiv hcl) (10 mg a day) and selective serotonin reuptake inhibitors including fluoxetine, sertraline and paroxetine.
Since the mechanisms of these reactions are not fully understood, it seems prudent, in general, to avoid this combination of ELDEPRYL (Cognitiv hcl) and tricyclic antidepressants as well as ELDEPRYL (Cognitiv hcl) and selective serotonin reuptake inhibitors. At least 14 days should elapse between discontinuation of ELDEPRYL (Cognitiv hcl) and initiation of treatment with a tricyclic antidepressant or selective serotonin reuptake inhibitors. Because of the long half-lives of fluoxetine and its active metabolite, at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of treatment with ELDEPRYL (Cognitiv hcl) .
Rated Cognitiv for Depression Report
I take 10mg once a day. I have been taking it for over a year. This has been my wonder drug. I have taken Wellbutrin, Lexapro, and other meds in the past.
Before taking Cognitiv
Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking Cognitiv it is important that your doctor or pharmacist knows:
- If you are pregnant or breast-feeding.
- If you have a stomach or duodenal ulcer.
- If you have high blood pressure, an irregular heartbeat, or angina pain.
- If you have had a mental health problem (in particular, psychosis).
- If you have a problem with the way your liver works, or with the way your k >
Can Cognitiv cause problems?
Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with Cognitiv. You will find a full list in the manufacturer's information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.
Overdose with Non-Selective MAO Inhibition
NOTE: This section is provided for reference; it does not describe events that have actually been observed with Cognitiv in overdose.
Characteristically, signs and symptoms of non-selective MAOI overdose may not appear immediately. Delays of up to 12 hours between ingestion of drug and the appearance of signs may occur. Importantly, the peak intensity of the syndrome may not be reached for upwards of a day following the overdose. Death has been reported following overdosage. Therefore, immediate hospitalization, with continuous patient observation and monitoring for a period of at least two days following the ingestion of such drugs in overdose, is strongly recommended.
The clinical picture of MAOI overdose varies considerably; its severity may be a function of the amount of drug consumed. The central nervous and cardiovascular systems are prominently involved.
Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.