Desyrel 100 mg

(See also Precautions, Drug Interactions.) In vitro drug metabolism studies reveal that trazodone is a substrate of the cytochrome P450 3A4 (CYP3A4) enzyme and trazodone metabolism can be inhibited by the CYP3A4 inhibitors ketoconazole, ritonavir, and indinavir. The effect of short-term administration of ritonavir (200 mg twice daily, 4 doses) on the pharmacokinetics of a single dose of trazodone (50 mg) has been studied in 10 healthy subjects. The C_max of trazodone increased by 34%, the AUC increased 2.4-fold, the half-life increased by 2.2-fold, and the clearance decreased by 52%. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were co-administered.

Carbamazepine induces CYP3A4. Following co-administration of carbamazepine 400 mg/day with trazodone 100 mg to 300 mg daily, carbamazepine reduced plasma concentrations of trazodone (as well as mCPP) by 76 and 60%, respectively, compared to pre-carbamazepine values.

Absorption: Trazodone is well absorbed after oral administration with peak plasma levels obtained within 0.5 to 2 hours after ingestion. Absorption is somewhat delayed and enhanced by food. Trazodone is 89-95% protein bound in vitro at concentrations attained with therapeutic doses.

Metabolism: In vitro studies in human liver microsomes show that trazodone is metabolized to an active metabolite, m-chlorophenylpiperazine (mCPP) by cytochrome P450 3A4 (CYP3A4). Other metabolic pathways that may be involved in metabolism of trazodone have not been well characterized.

Elimination: Approximately 60-70% of ¹⁴C-labelled trazodone was found to be excreted in the urine within two days and 9-29% in feces over 60-100 hours.

In some patients DESYREL may accumulate in the plasma.

In vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with CYP3A4 inhibitors. Ritonavir, a potent CYP3A4 inhibitor, increased the C_max, AUC, and elimination half-life, and decreased clearance of trazodone after administration of ritonavir twice daily for 2 days. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were co-administered. It is likely that ketoconazole, indinavir, and other CYP3A4 inhibitors such as itraconazole or nefazodone may lead to substantial increases in trazodone plasma concentrations with the potential for adverse effects. If trazodone is used with a potent CYP3A4 inhibitor, a lower dose of trazodone should be considered.

Carbamazepine reduced plasma concentrations of trazodone when co-administered. Patients should be closely monitored to see if there is a need for an increased dose of trazodone when taking both drugs.

Trazodone may enhance the response to alcohol and the effects of barbiturates and other CNS depressants and patients should be cautioned accordingly.

Increased serum digoxin and phenytoin levels have been reported to occur in patients receiving DESYREL concurrently with either of those 2 drugs. Little is known about the interaction between DESYREL and general anesthetics; therefore, prior to elective surgery, DESYREL should be discontinued for as long as clinically feasible.

Because it is not known whether an interaction will occur between DESYREL and MAO inhibitors, administration of DESYREL should be initiated very cautiously with gradual increase in dosage as required, if an MAO inhibitor is given concomitantly or has been discontinued shortly before medication with DESYREL is instituted.

DESYREL may cause hypotension including orthostatic hypotension and syncope; caution is required if it is given to patients receiving antihypertensive drugs and an adjustment in the dose of the antihypertensive medication may be required.

Because of the absence of experience, concurrent administration of electro-shock therapy should be avoided.

There have been reports of increased and decreased prothrombin time occurring in warfarinized patients who take DESYREL.

Since DESYREL and/or its metabolites have been detected in the milk of lactating animals, it should not be administered to nursing mothers unless the potential benefits justify the possible risks to the child.

There is sufficient experimental evidence to conclude that chronic administration of those psychotropic drugs, such as trazodone, which increase prolactin secretion has the potential to induce mammary neoplasms in rodents under appropriate conditions. Tissue culture experiments indicate that approximately 33% of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer.

Although disturbances such as galactorrhea, amenorrhea, gynecomastia and impotence have been reported, the clinical significance of elevated serum prolactin levels or increased secretion and turnover are unknown for most patients. Neither clinical studies nor epidemiological studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis: available evidence is considered too limited to be conclusive at this time.

The safety and effectiveness of DESYREL in children below the age of 18 have not been established.

The possibility of suicide in depressed patients remains during treatment and until significant remission occurs. Therefore, the number of tablets prescribed at any one time should take into account this possibility, and patients with suicide ideation should never have access to large quantities of trazodone.

Episodes of grand mal seizures have been reported in a small number of patients. The majority of these patients were already receiving anticonvulsant therapy for a previously diagnosed seizure disorder.

Since the safety and use of DESYREL in pregnant women has not been established, it should not be used in women of childbearing potential unless, in the opinion of the physician, the expected benefits justify the potential risk to the fetus.

Safety of Driving: Since DESYREL (trazodone hydrochloride) may impair the mental and/or physical abilities required for performance of potentially hazardous tasks, such as operating an automobile or machinery, the patient should be cautioned not to engage in such activities while impaired.

It is recommended that white blood cell and differential counts should be performed in patients who develop sore throat, fever, or other signs of infection or blood dyscrasia and DESYREL should be discontinued if the white blood cell or absolute neutrophil count falls below normal.

Each orange, round, biconvex tablet, engraved with “DESYREL” and “BL” around the periphery on one side and with a bisect bar on the other side, contains: trazodone HCl 50 mg. Nonmedicinal ingredients: cornstarch, dibasic calcium phosphate, FD&C yellow No. 6 aluminum lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and sodium starch glycolate. Bottles of 100 and 250.

Each white to off-white, round, biconvex tablet engraved with “DESYREL” and “BL” around the periphery on one side and with a bisect bar on the other side, contains: trazodone HCl 100 mg. Nonmedicinal ingredients: cornstarch, dibasic calcium phosphate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and sodium starch glycolate. Bottles of 100.

Each orange, rectangular, flat-faced, bevel-edged tablet, with bisect/trisect scoring, engraved on one side with a “BL” logo on the left segment, a blank center segment, and a “BL” logo on the right segment, the other side engraved with a “50" on each segment contains: trazodone HCl 150 mg. Nonmedicinal ingredients: FD&C yellow No. 6 aluminum lake, magnesium stearate, microcrystalline cellulose, pregelatinized starch and stearic acid. Bottles of 100.

The DIVIDOSE 150 mg tablet design makes dosage adjustments easy. Each tablet can be broken accurately to provide any of the following dosages: 50 mg (one-third of a tablet); 75 mg (one-half of a tablet); 100 mg (two-thirds of a tablet); 150 mg (the entire tablet). Instructions: To break a DIVIDOSE tablet accurately and easily, hold the tablet between your thumbs and index fingers close to the appropriate tablet score (groove). Then with the tablet score facing you, apply pressure and snap the tablet segments apart.

nausea, vomiting, diarrhea, gastrointestinal discomfort, anorexia, increased appetite.

tremor, headache, ataxia, akathisia, muscle stiffness, slurred speech, retarded speech, vertigo, tinnitus, tingling of extremities, paresthesia, weakness, grand mal seizures (see Precautions), and, rarely impaired speech, muscle twitching, numbness, dystonia and involuntary movements.

drowsiness, fatigue, lethargy, retardation, lightheadedness, dizziness, difficulty in concentration, confusion, impaired memory, disorientation, excitement, agitation, anxiety, tension, nervousness, restlessness, insomnia, nightmares, anger, hostility and, rarely, hypomania, visual distortions, hallucinations, delusions and paranoia.

dry mouth, blurred vision, diplopia, miosis, nasal congestion, constipation, sweating, urinary retention, increased urinary frequency and incontinence.

priapism (see Warnings), decrease and, more rarely, increase in libido, weight gain and loss, and rarely, menstrual irregularities, retrograde ejaculation and inhibition of ejaculation.

aching joints and muscles, peculiar taste, hypersalivation, chest pain, hematuria, red, tired and itchy eyes.

skin rash, itching, edema, and, rarely, hemolytic anemia, methemoglobinemia, liver enzyme alterations, obstructive jaundice, leukocytoblastic vasculitis, purpuric maculopapular eruptions, photosensitivity and fever.

orthostatic hypotension, hypertension, tachycardia, palpitations, shortness of breath, apnea, syncope, arrhythmias, prolonged P-R interval, atrial fibrillation, bradycardia, ventricular ectopic activity (including ventricular tachycardia), myocardial infarction, cardiac arrest and conduction block.

Overdosage of DESYREL (trazodone hydrochloride) may cause an increase in incidence or severity of any of the reported adverse reactions, e.g. hypotension and excessive sedation. In one known suicide attempt, the patient presented with symptoms of drowsiness and weakness 3 hours after ingesting 7.5 g (12.5 times the maximum daily dose) of trazodone. Recovery was uneventful. Death by deliberate or accidental overdosage with trazodone alone has not been reported.

There is no specific antidote for trazodone. Management of overdosage should, therefore, be symptomatic and supportive. Any patient suspected of having taken an overdosage should be admitted to hospital as soon as possible and the stomach emptied by gastric lavage. Forced diuresis may be useful in facilitating elimination of the drug.

If used in the elderly, doses not exceeding one-half the recommended adult dosage should be used, with adjustments made depending on tolerance and response.

Because safety and effectiveness in children have not been established DESYREL is not recommended in the pediatric age group.

The recommended initial dose is 150 to 200 mg daily, in 2 or 3 divided doses. DESYREL (trazodone hydrochloride) should be taken shortly after a meal or light snack in order to reduce the incidence of adverse reactions. The initial dose may be increased according to tolerance and response by increments of 50 mg, usually up to 300 mg daily in divided doses. In some patients, doses up to 400 mg daily and rarely up to 600 mg daily in hospitalized patients, may be required. Occurrence of drowsiness may require the administration of a major portion of the daily dose at bedtime or a reduction of dosage.

Once an adequate response has been achieved, the dosage may be gradually reduced, with adjustment depending on therapeutic response. During prolonged maintenance therapy the dosage should be kept at the lowest effective level.