Interacting drugs -

Summary

+Carbamazepine-

 Cimetidine/ Danazol/diltizem/ macrolides except azithromycin/ prpoxyphene/ verapramil  +

inhibited carbamazepine metabolism , elevated carbamazepine level and toxicity.

Antihistamine- non sedating +

 terfenadine increased carbamazepine level

Barbiturate/ primidone +

Carbamexepine + primidone

  concurrent use may lower carbamazeoine level, no loss of seizure control 

Charcoal + carbamazepine

charcoal decrease GI absorption of carbamazepine

Felbamate + carbamazepine

Carbamazepine + felbamate

serum level of either agent decreased

Hydantoins + carbamazepine

carbamazepine - hydantoin

 both increased and decreased hydantoin level as well as decreased carbameoine level

 Fluoxetine (SSRIs) / fluvoxamine+

 carbamazepine levels increased, increased toxicity

 Theophylline + carbamazepine

carbamazepine + theophylline

carbamaz level decreased, theophy incres.or or decreased

Tricyclic antidepressants + carbamazepine

carbamazepine + Tricyclic antidepressants

 carbamazepine levels may be increased. TCA  levels  levels increased

 Valproic acid +Carbamazepine

Carbamazepine + valproic acid

  valporic acid plasma levels decreased by carbamazepine Carbamazepine.  However, valproic acid prolong carbamaz half-life

Carbamazepine +  Acetaminophen

carbamaz increase metabolism of acetaminophen

Carbamazepine + Anticoagulants

 carbamaz increase metobolism, however, hypothrombic effect decreased

Carbamazepine  + Contraceptives, Oral

 decrease in QC effectiveness - unintended pregnancy

Carbamazepine + Doxycycline

 doxycline half life reduced with coadministration

Carbamazepine+ Haloperidol

 haloperidol serum level decreased by carbamaz

Carbamazepine + Lithium

 increased CNS toxicity with carbamaz concomittant admin

Carbamazepine + Non depolarizing neuromuscular blockers

decr carbamz cause reversal of neuromuscular blocking effect

Carbamazepine + Posterior pituitutitary hormones

 carbamaz potentiate antidiuretic of vassopressin, lypresin or desmopressin

Carbamazepine + Succinamides

 plasma level of succinamide reduced by carbamaz

Epilepsy,trigeminal neuralgia

Anticonvulsants incude-

 BARBITURATES - OXAZOLIDINEDIONES- MISCELLANEOUS- Phenobarbitone Paramethadione Lamotrigine Trimethadione Primidone

HYDANTOINS- Valproic acid Phenytoin

BENZODIAPINES- Cabamazepine Mephenytoin Clonazepam Phenacemide Ethotoin Clorazepate Felbamate Diazepam Gabapentin

SUCCINIMIDES- Ethosuximide Methsuximide Phensuximide

REFER PHENYTOIN SODIUM -

Most frequent-

Dizziness,drowsiness, unsteadiness, nausea, vomiting.

To minimise such reactions initiate therapy at low doses.

Hematologic-

Alpastic anemia, leukopenia, bone marrow depression, acute intermittant porphria.

Pulmonary-

Pulmonary hypersensitivity characterised by fever, dyspnea, pneumonitis or pneumonia

Hepatic-

Abnormal liver function tests, cholestatic/hepatocellular jaundice, hepatitis

GU-

Urinary frequency,, acute rinary retention, oliguria with hypetension, renal failure, azotemia, impotence, albumineria, glycosuria, elevated BUN, microscopic deposits in urine

CNS-

Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus, hyperracusis, behavoiural changes in children, paralysis and other symptoms of cerebral arterial insufficiency

Dermatologic-

Pruritic and erythematous rashes, urticaria, Stevens-Johnson syndrome, photosentivity, reactions, alterations in pigmentations, exfoliative dernatitis, alopecia, diaphoresis, erytrhema multiforme and nosudum, purpura, aggrevation of deseminated lupus erythematous, and toxic epidermal necrolysis, (Leyells syndrome).

Discontinuation of the therapy may be necessary

GI-

Nausea, vomiting, gastric distress, abdominal pain, diarrhea, constipation, anorexia, dryness of mouth or pharynx, glossitis and stomatitis

Cardiovascular-

Congestive heart failure, aggrevation of hypertension, hypotension, syncope and collapse, edema, primary thrombophlebitis, recurrence of phlebitis, aggravation of coronary artery disease, arrhythmias, AV block, adenopathy,or lymphadenopathy. Some cardiovascular complications have resulted in fatalities

Ophthalmic-

Transceint diplopia and oculomotor disturbances, nystagmus, scattered, punctate cortical lens opacities, conjuntivitis.

Musculoskeletal-

Aching joints and muscle leg cramps

Metabolic-

Fever and chills, inapropiate antidiuretic hormone secretion syndrome (SIADH)

Hypersens.A.V.conduction abnormalities,porphyria.

Special precautions:

Monitoring- Perform baseline liver function tests and periodic evaluations. Discontinue drug immediately if liver dysfunctioin occurs. Obtain baseline and periodic eye examinatins Monitering of blood levels may be particularly useful in cases of dramatic increase in seizure frequency, for verification of compliance and in determining the cause of toxicity when more than one drug is being used.

Special risk patients- prescribe carbamazepine only after benefit-to -risk appraisal in patients with a history of cardiac,hepatic or renal damage, adverse hematological reaction to other drugs, interrrupted courses of therapy with the drug

Hazardous tasks- may produce drowsiness or blurred vision, patients should observe caution while driving or performing tasks requiring alertness, coordination or physical dexterity.

Warnings-

Minor pain- this drug is not a simple analgesic. Do not use for relief of minor aches or pain. Hematologic- patients with a history of adverse hematologic reaction to any drug may be particularly at risk. Glaucoma- carbamazepine has shown mild anticholinergic activity ,therefore use with caution in patients with increased intraocular pressure

CNS effects- because of the drugs relationship to other tricyclic compounds the possibility of activating latent psychosis, confusion or agitation in elderly patients exists.

Pregnancy- use only when clearly needed. and when potential benefits outweigh the unknown potential hazards to the fetus.

Lactation- because of the potential for serious adverse reactins, decide whether to discontinue nursing or to discontinue the drug, taking into consideration the importance of the drug to the mother.

Children- safety and efficacy for use in children < 6 years of age have not been established.

Indications:

Epilepsy,trigeminal neuralgia

Dosage: Individualise dose. A initial low daily dose with gradual increase is advised. Adult and children over 12 years. Initial dose 200mg twice daily. Increase at weekly intervals to 200mg 3 or 4 times a day . Do not exceed 1000mg/day in Children 12 to 15 years or 1200mg/day in patients over 15 years.

Overdosage- Symptoms Lowest known lethal dose- Adults- 60g ( 39 year old man) Highest known doses survived- Adults- 30g (31 year old woman ) Children- 10g ( 6 year old boy) Small children- 5 g ( 3 year old girl) Signs and symptoms after 1 to 3 hours

Neuromuscular disturbances are most prominent. Cardiovascular disordes are generally mild and severe cardiac complications occur only when very high doses (> 60g) have been ingested. Respiratory- Irregular breathing, respiratory depression,

Cardiovascular- Tachycardia, hypotension or hypertension,shock, conduction disorders CNS- Impaired consciousness ranging from deep coma, convulsions, especially in small children, motor restlessness, muscular twitiching ,tremor, athetoid movements, opisthotonos, ataxia, drowsiness, mydriasis, nystagmus, adiadochokinesia, EEG may slow dysrhythmias

GI/GU-Nausea, vomting, anuria, or oliguria, urinary retention. Lab findings- isolated instances of overdosage have indcluded leukocytosis, reduced count, glycosuria and atenonuria.

Treatment

1.There is no specific antidote.

2. Charcoal administration is effective in increasing the total body clearance of carbamazepine.

3. Dialysis is indicated only in severe poisoning associated with renal failure.

4. Replacement tranfusion is indicated in severe poisoning in small children

5. In treating convulsions, diazepam or barbiturates may aggravate respiratory depression (especially in children) hypotension and coma.

6. Do not use barbiturates if MAO inhibitors have also been taken by the patient either in overdosage or in recent therapy ( within a week)

7. Monitor respiration ECG blood pressure, body temperature, pupilary reflexes and kidney and bladder function for several days.

8. Treatment of blood count abnormalities- If evidence of significant bone marrow depression develops, discontinue drug, perform daily CBC, platelet and reticulocyte counts, perform bone marrow aspiration, and trephine biospy immediately and repeat with sufficient frequency to monitor recovery.

 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.

Name:

Carbamazepine Classification:

Anti-convulsant Patent position:

Major brands CARBATOL TORRENT MAZETOL SG PHARMA TEGRETOL HIND-CIBA GEIGY Domestic production 93/94 240kg Imports 93/94 35.5T Rs. 50miln Rs. 1352/kg Raw materials:

1.Chloromethyl nitrobenzene

2.Nitrobenzyl chloride

3.Dihydr 5h dibenz azepine

4.Dibenz azepine or imidobenzyl

5.Iminostilbene

6.Methyl thio urea

7.Iminodibenzyl carbonyl chloride ** **

concessional duty

Manufacturers: 1.Torrent pharma Ahmedabad- 6T -2/92

CARBAMAZEPINE-- ANTICONVULSANT

1.May produce drowsiness,dizziness or blurred vision,patients should observe caution while driving or performing tasks requiring alertness,coordination or physical dexterity.

2. Notify physician if any of the following occurs- Unusual bleeding,or bruising, jaundice, abdominal pain, impotence, CNS disturbances,edema, fever, chills, sore throat, or ulcers in the mouth.

3.May cause GI upset,take with food.

4.Allergy- Tell your doctor if you ever had any unusual or allergic reaction to carbamazepine or to any of the tricyclic antidepressants such as amitriptyline, amoxine, clomiprime, desipramine, doxepin, imipramine, nortriptyline, protiptyline, or trimipramime. Also tell your doctor if you are allergic to any other substances such as foods, preseratives or dyes.

5. Pregnancy- Carbamazepine has not been studied in pregnant women.There have been reports of babies having low birth weight, small head size, skull and facial defects,under developed fingernails, and delays in growth when their mothers had taken carbamazepine in high doses during pregnancy. Use of carbamazepine during pregnancy should be discussed with your doctor.

6. Breast feeding- Carbamzeoie passes into breast milk and in some cases may receive enough to cause unwanted effects. In anmal studies carbamazepine has affected the growth and appearance of the nursing babies

7. Children- Behaviour changes ae more likely to occur in children

8. Older adults- Confusion, restlessness, and nervousness, irregular , pounding or unusually slow heart beat and chest pain may be especially likely to occur n elderly patients who re usually more sensitive than younger adults to the of carbamazepine of effects

9.Other medicines- When you are taking carbamazepine it is important that your doctor knows if you are taking any of the following- Anticoagulants -effects of anticoagulants may be decreased, monitoring of blood clottig time may be necessary during and after carbamaziine treatment.

Cimetidine -blood levels of carbamazine may be incr , leading to an increase in side effects. Clarithromycin - blood levels of carbamazipine may be incr ,increasing the risk of unwanted effects Corticosteroids - effects of corticosteroids may be decreased

Diltiazem or Erythromycin or Propoxyphene or Verapramil - blood levels of carbamazepinemay be incr , these medicines should not be used with carbamzepine Estrgens or Oral contraceptives containg estrogens or Quinidine -efects ofthese medicines may be decreased , use f non hormonal method of birth control or an oral contraceptives contg only a progestin be necessary Isoniazid - risk of serioussideeffects may be increased

MAOI- taking carbamazepine while you are taking or within 2 weeks of MAOI may cause sudden high body temperature, extremely high blood pressure and severe convulsions . Atleast 14 days should should be allowed between stopping treatment with the medicine and starting treatment with the other. Other anticonvulsants -effects of these medicines may be decreased. In addition, if these medicines and carbamazipine are used together during pregnancy, the risk of birth defects may be increased. Risperidone- effects of risperidone may be decreased Tricyclic antidepressants- CNS depressants effects ofcarbamzepine may be decreased , seizures may occur more frequently.

10. Other medical problems- Tell your doctor if you have any other medical problems especially - Alcohol abuse -drinking alcohol may decrease the effectiveness of carbamazepine Behavioural problems or Glaucoma or Heart or blood vessel disease or Problems with uriation - carbamazepine may make the condition worse.

Diabetes mellitus - carbamazepine may cause increased urine glucose levels Kidney disease or Liver disease -higher blood levels of carbamzepine may result, increasing the chance of side effects.

11. Dosing- Dose of carbamazepie may bedifferent fordifferent partiets. Follow your doctors incstructions

12. Missed doses- If you miss a dose ofthis medicine take it as soon as possible. However, if it is almost time for the next dose, skip themissed dose and go back to your normal schedule. Do not double doses.

13. Storage- Keep the medicines outof reach of children Store away from direct heat and sunligt Do not store medicines under the kitchen sink or in in bath room cupboard or in damp places. Moisture and heat will cause the medicine to break down. Keep the liquid form of medicine from freezing. Do not keep outdated medicines or medicines no longer in use. Make sure that all discarded medicines are kept away from children.

ANTICONVULSANTS INCLUDES - BARBITURATES - OXAZOLIDINEDIONES- MISCELLANEOUS-

Pharmacology:

Carbamazepine is an iminostilbene derivative chemically related to the tricyclic antidepressants and unrelated to other anticonvulsant. Its mechanism of action is unknown. Pharmacokinetics Carbamazepine is adequately absorbed,with peak levels acheived in 4 to 5 hours following administration. Both suspension and tablets deliver equivalent amounts of drug to the systemic circulation,however,the suspension is absorbed faster than the tablet. Metabolism: Carbamazepine is metabolised in the liver to the 10,11-epoxide,which also has anticonvulsant activity.

Avoid grapefruit juice

Pregnancy:

Adverse effects have been observed in animal studies. Use only when clearly needed.

Lactation:

Concentration of carbamazepine in breast milk is approximately 60% of the maternal plasma concentration. Because of the potential for serious adverse reaction,decide to continue or discontinue nursing or discontinue the drug,taking into consideration the importance of the drug to the mother.

Chlidren:

Safety and efficacy for use in children below 6 years have not been established.