Depression 

Phenylpiperazine group - Nefazodone 

Coadministration with tefenadine or astemizole., hypersens to nefazodone.

Special precautions:

Postural hypotension- use nefazodone with caution in patients with known cardiovascular or cerbrovascular disease that could be exacerabated by hypotension ( eg. history of MI , angina, ischemic stroke ) and conditions that would predispose patients to hypotension (eg dehydration, hypovolemia, treatment with antihypertesive medication) Mania/hypomania- as with all antidepressants, use nefazodone cautiously in patients with a history of mania.

Suicide- the possibilityof a suicide attempt is inherent with depression and may persist until remission occurs. Closely supervise high-risk patients during initial therapy. Write prescriptions for the smallest quantity of nefazodone consistent with good patient management to reducethe risk of overdose.

Seizures- a recuurence of a petit mal seizure was observed in a patient receiving nefazodone, who had a history of seizures.

Priapism- Priapism has been reported with structurally related dru, trozodone. If patientspresent with prolonged or inappropriate erections, they should discontinue therapy immediately and consult their physician.

Bradycardia- treat patients with a recent MI orunstable heart disease with caution. Hepatic cirrhosis- in patients with cirrhosis of the liver, the aUC values of nefazodone and its metabolite HO-NEF were increased by about 25%. Drug absuse and dependence- Carefully evaluate patients for a history of misuse or abuse of nefazodone.

Warnings-

Long-term use- periodically reevaluate the long-termusefulness of the drug for the indivdual patient MAO inhibitors- it is recommended that nefazodone not be used in combination with an MAOI or within 14 days of discontinuing treatment with an MAOI. Allow atleast 1 week after stopping nefazodone before starting an MAOI.

Antihisatmines- it is recommended that nefazodone not be used in combination with either terfenadine or astemazole

Fertility impairment- a fertilty study in rats showed a slight increase in fertility at 200mg/day (aproximately 3 times the maximum human dose)

Elderly- observe the usual precautions innelderly patients who have concomittant medical illness or who are receving concomittant drugs.

Pregnancy- there ae no adequate and well controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to fetus.

Lactation- excercise caution when nefazodone is administered to a nursing woman.

Children- safety and efficacy in individuals < 18 years old have not been established

Approved by FDA on December 22, 1994

Indications:

Depression

Dosage:

Recommened starting dose is 200mg/day, adminstered in two divided doses. Effective dose range was 300 to 600mg/day. Several weeks of treatment may be necessary to obtain full antidepressant activity.

Overdosage-

Symptoms Nausea, vomiting and somnolence.

Treatment

1.There is no specific antidote for nefazodone.

2. Treatment should be symptomatic and supportive in the case of hypotension or excessive sedation.

3. Any patient suspected of having taken on overdose should have the stomach emptied by gastric lavage.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

NEFAZODONE HCL- ANTIDEPRESSANTS 

1. Several weeks of treatment may be required to obtain the full antidepressant effect. It is important to continue full treatment as directed.

2. Caution patients about operating hazardous machinery including automobiles

3. Advise patients to notify physician if they become pregnant or intend to become pregnant during therapy or if they are breast feeding an infant.

4. Advise patients to inform physician or pharmacist if they are taking over the counter drugs.

5.Combinations with alprozolam or triazolam and concomittant use with astemaizole or terfenadine is contraindicated

6. Notify physician, if the patient develops a rash, hives, or related allergic phenomenon.

7. Allergies- Tell your doctor if you have ever had any unusual or allergic reaction to Tacrine or to wound antiseptic. Also tell your doctor if you are allergic to any other substances, such as foods, preservatives or dyes.

8.Pregnancy - Studies on effects in pregnancy have not been done in either humans or animals

9.Breast feeding- It is not known whether tacrine passes into breast milk. However use of tacrine not recommended in nursing mothers

10. Children- Not reported

11. Elderly- Studies on tacrine have been done only in middle-aged and older patients. Information on the effects of tacrine is based on these patients

12. Other medicines - Let your doctor know what other medicines you are taking, so that he can advice you accordingly. Cimetidine - cimetidine may cause higher blood levels of tacrine which may increase the chance of side effects. Inflammation or pain medicine except narcotics - sdtomach irritation may be increased

Neuromuscular blocking agents - tacrine may increase the effects of these medicines, your doctor may change the dose of tacrine you have surgery Smoking tobacco- smoking may cause lower blood levels of tacrine, which may decrease the effects of tacrine, if you smoke your doctor may need to change the dose of tacrine. Theophylline- tacrine may cause higher blood levels of theophyliine, which may increase the chance of side effects Your doctor may need to change the dose of theophylline

13. Other medical problems - Tell your doctor if you have any other medical problems especially - Asthma or Heart problems , including slow heart beats or hypotension, low blood pressure or Intestinal blockage or Liver disease or Parkinsons disease or Stomach ulcer or Urinary tract blockage or difficult urination - tacrine may make these conditions worse Brain disease other or Epilepsy or history of seizures or Head injury with loss of consciousness- tacrine may cause seizures

14. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

15. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

16. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Pharmacology:

Nafazodone is an antidepressant with a chemical structure unrelated to well known antidepressants. The mechanism of action ofvnefazodone is unknown. It inhibits uptake of serotinin and norepinehrine

Pharmacokinetics:

Nefazodone is rapidly and and completely absorbed , but is subject to extensive mertabolism so that its absolute bioavailability is low. Food delays absorption and decreases the bioavailability. Peak plasma concentrations occur at about 1 hour. Half-life is 2 to 4 hours

Food delays absorption and reduces bioavailability

Pregnancy: Use during pregnancy only if needed.

Lactation: Excercise caution when nefazodone is administered to a nursing woman.

Children- Safety and efficacy in individuals < 18 years old have not been established