Interacting drugs - summary

 Bupropion + Levodopa

Higher incidence of adverse experiences with concurrent use of threse agents. use small doses initially and small gradual increase in bupropion

 MAOI + Burpropion

Bupropion acute toxicity is enhanced by phenezine.   At least 14 days should elapse between discontinuation of an MAOI and initiation of bupropion

Discontinuation-

Adverse reactions caused discontinuation  in approx 10% of patients and volunteers
The most common events causing discontinution-
Neuropsychiatric disturbnces , primary agitation and abnormalities in mental status 3 %
GI disturbances, primary nausea and vomiting 2%
Neurological disturbances , primary seizures, headache and sleep disturbances 2%
Dermatological problems , primary rashes 1 %
Many of these occurred at doses that exceeded the recommended daily dose

GI- 

stomatitis 1%, tooth ache, bruxism, gum irritation , oral edema  dysphagia, thirst disturbances, liver damage/ jaundice 1%, glossitis, rectal complaints colitis, GI bleeding , stomach ulcer, intestinal peforation < 0.1%

Cardiovascular -

  Edema 1%, ECG  abnormalites (premature beats nd non specific ST-T  changes  chest pain, shortness of breath/dyspnea 1%,
pallor, phlebitis, flushing , myocardial infarction < 0.1%

Dermatologic -

rashes 1%, alopecia, dry skin 1%,acne, hair color change  hirsutism < 0.1%

Endocrine -

Gynaecomastia  1%,    glycosuria , hormone level change <  1%

GU -

Nocturia 1% vaginal irritation, testicular swelling, urinary tract infection, painful erection, retarded ejaculation 1%  dysuria, enuresis, urinary incontinence, menopause, ovarian disorder, pelvic infection, cystisis,   dyspariea, painful ejaculation < 0.1%

Hematologic -

Anemia, pancytoma, lymphadenopathy < 0.1%

Psychiatric -

Mania/hypomania, increased libido, hallucinations, decreased sexual function,
  depression 1%

Respiratory -

Bronchitis, shortness of breath/dyspnea  1%,   epistaxis, rate or rhythm dosorder, pneumonia, pulmonary embolism < 0.1%

Special senses -

Visual disturbance 1%, diplopia <  1%
 
Musculoskeletal -

Arthalgia , myalgia, muscle rigidity

Miscellanous- 

 Flu like syndrome 1%, non specific pain  1%,   body odour, surgically related pain, infection, medication reaction,  musculoskeletal chest pain  overdose < 0.1%

Hypersensitivity to the drug, seizure disorder.

Special precautions:

Drug abuse dependence- evidence suggests that the recommended daily dosage of bupropion when administered in divided doses is not likely to be especially reinforcing to amphetamine or stimulant abusers.

CNS syndrome- a substantial proportion of patients experience some degree of increased restlessness, agitation, anxiety, and insomnia especially after initiation of treatment.

Activation of psychosis or mania- patients during the depressed phase of theirillness may activate latent psychosis in susceptible patients.

Suicide- posibility of a suicide attempt is inherent in depression, accordingly, write prescriptions for the smaller number of tablets consistent with good patient management

Heart disease- exercise care in patients with a recent history of myocardial infarction or unstable heart disease.

Warnings-

Seizures- bupropion is associated with seizures in about 0.4% of patients treated at doses up to 450mg/day. .

Recommendations for reducing seizure risks-

1.The total daily dose does not exceed 450mg.

2. The daily dose is administered 3times daily. which each single dose not to exeed 150mg to avoid peak concentrations of bupropon or its meatbolites.

3. The rate of incrementation of dose is very gradual

Hepatotoxicity- there is no clinical evidence that bupropion is hepatoxic in humans

Renal/hepatic function impairment- closely monitor for possible toxic effects of elevated blood and tissue levels of drug and its metabolites

Pregnancy- Use during pregnancy only ifclearly needed.

Lactation- Becase of the potential for serious adverse reaction to nursing infants, decide whether to discontinue nursing or discontinuethe drug taking into account the importance of the drug to the mother.

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

Date of Approval      2001

Indications:

Depression

Dosage:

Adults- 300mg/day given 3 times a daily. Start at 200mg/day, given as 100mg given twice daily. This may be increased to 300mg given as 100mg 3 times daily.

Overdosage- Symptoms

Hallucinations,grand mal seizure, loss of consciousness, and tachycardia. Although most patients recovered without sequalae, deaths have been reported rarely in patients ingesting massive doses; multiple uncontrolled seizures, bradycardia,cardiac failure and cardiac arrest prior to death were reported in these patients.

Treatment

1. Hospitalize

2. If the patient is conscious , induce vomting with syrup of ipecac.

3. Administer activated charcoal every 6 hours during the first 12 hours after ingestion and obtain baseline laboratory values.

4. Perform ECG and EEG monitoring for the next 12 hours.

5. Provide adequate fluid intake.

6. If the patient is stuporous, comatose or convulsing, perfom airway intubation prior to undertaking gastric lavage

7. Although there is little clinical experience,lavage is likely to be of benefit within the first 12 hours of ingestion since absorption of the drug may not yet be complete

. 8. Because diffusion of bupropion from tissue to plasma may be slow, dialysis may be of minimal benefit several hours after overdose.

9. Treat seizures with IV benzodiazepines and other supportive measures.

 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. 

BUPROPION HCL- ANTIDEPRESSANTS

1.Take in equally divided doses 3 or times a day to minimise the risk of seizure.

2. May impair ability to perform tasks requiring judgement or motor and cognitive skills. Patients should refrain from driving an automobile or operating complex hazardous machinery

. 3. Use and cessation of alcohol may alter the seizure threshold. Minimise consumption of alcohol.

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

5.Pregnancy - Studies on effects in pregnancy have not been done in pregnant women. However, bupropionn has not been reported to cause birth defects or problems in animal studies.

6.Breast feeding- Bupropion passes into breast milk. Because it may cause unwanted effects in babies , use of bupropion is not recommended during breast feding

7. Children -Studies done only on adult persons and there are no specific information comparing use in children with use in other age groups.

8. Elderly- This medicine has been tested in a limited nunmber of patients 60 years of age and older and has not been been shown to cause to different side efects or problems in older people than it does in younger adults

9. Other medicines - Let your doctor know what other medicines you are taking, so that he can advice you accordingly. Alcohol or Antipsychotics medicines or Fluoxetine or Lithium or Maprotiline or Trazadone or Tricyclic antidepressants - using these medicines with bupropion may increase the risk of seizures

 10. Other medical problems - Tell your doctor if you have any other medical problems especially - Anorexia or Brain tumor or Bulima or Head injury or Seizure disorder - risk of seizures may be increased when bupropion is taken by patients with these conditions

  11. 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.

12. 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.

13. 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:

Bupropion,an antidepressant of the aminoketone class is chemically unrelated to other avialable antidepressant agent Its structure closely resembles that of diethylpropion; it is realted to phenylethylamines.

Bupropion does not inhibit monoamine oxidase. Compared to tricyclic antidepressants, it is a weak blocker of neuronal uptake of serotonin and norepinephrine.

Pharmacokinetics:

Following oral admin, peak plasma concentrations are usually acheived within 2 hours. Six hours after a single dose, peak plasma concentrations are about 30% of peak concentrations

Pregnancy:

Use during pregnancy only if required

Lactation:

Because of the potential for serious adverse reaction to nursing infants, decide whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children-

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