Alzheimers disease 

Tacrine Hcl - ( Tetrahydroaminacridine - THA ) - Miscellaneous Psychotherapeutic agents

Most common-

Transaminase elevations were the most common reason for withdrawal during
treatment ( 8% of treated patients)

The most common adverse events were elevated transaminasses, nausea, vomiting, diraahea,dyspepsia, myalgia, anorexia and ataxa. Of these events, nausea, diarrhea, dyspepsia and anorexiaappeared to be dose - dependent

Elevated transaminases,nausea, vomiting, diarrhea, dyspepsia, and anorexia.

Chill, fever, malaise, peripheral edema, dehydration, weight increase, cachexia, generalised edema, heat exhaution, death.

Hypotension, hypertension heart failure, myocardial infraction, angina pectoris, cerebrovascular accident, transceint ischemic atacks, phlebitis, palpitation, venous insufficiency.

Glossitis, gingivitis, dry mouth, or throat, stomatitis, increased salivation, dysphagia, esophagitis, gastritis, gastroenteritis, GI haemorrhage stomach ulcer.

Hypersensitivity to tacrine or acridine derivatives.

Special precautions:

Monitoring serum transaminase levels every other week for at least the first 16 weks following initiation of treatment, after which monitoring may be decreased to monthly for 2 months every 3 months thereafter. \

Hematology- the total clinical experience of in > 8000 patients does not indicate a clear association between tacrine treatment and serious white count abnormalities Monitoring- repeat aul monitoring sequence in the event that a patient suispends treatment with tacrine for > 4 weeks.

If transaminase elevations occur modify the dose.

Warnings-

Anesthesia- tacrine is likely to exaggerate sucinylcholine -ytpe muscle relaxation during anesthesia. Cardiovascular conditions- because ofits cholinemimetic action,tacrine may have vagotonic efects on the heart rate (eg. bradycardia).

This action may bepaticularly important to patients withconduction abnormalities, bradyarrhythmias or a -sick sinus syndrome-.

GI disease/dysfunction- tacrine is an inhibitor of cholinesterase and may be expected to increase gastric acid secretion due to increased cholinergic activity. Closely monitor patients at increased risk of developing ulcers (eg. those with a history of ulcer disease or those receiving concurrent NSAIDs for symptoms of active ocult GI bleeding.

Hepatic effects- prescribe with care in patients with current evidence or history of abnormal liver function indicated by significant abnormalities of serum transaminase (ALT, AST, bilirubin, and gamma -glutamyl transpeptidase (GGT) levels.

Monitoring- monitor serum transaminase levels ( especially ALT) every other week for at least the first 16 weeks following initiation of treatment, after which monitoring may be decreased to monthly for 2 months and every 3 months therafter.

Rechallenge- patients who are required to discontinue treatment because of transaminase elevations may be rechallenged once transaminase levels return to within normal limits.

GU effects- cholinomimetics may cause bladder outflow obstruction Seizures- cholinomimetics are believed to have some potential to cause generalized convulsions, seizure activity may however alsobe a manifestation of Alzaheimers disease.

Pulmonary conditions- because of its cholinemimetic action, use tacrine with care in patients with a history of asthma. Carcinogenesis/ mutagenesis- the fact that tacrine belongs to a chemical class (acridines ) containing some members which are animal carcinogens, suggest that tacrine may be carcinogenic.

Pregnancy-

it is not known whether tacrine can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.

Lactation-

It is not known whether this drug is excxreted inn breast milk. Children- there are no adequate and well controlled to document the safety and efficacy of tacrine in any dementing illness occuring in children

Approved by FDA on September 9, 1993

  For treatment of dementia  in patiients with alzhelners  disease of  mild                                   to moderate  severity

Alzheimers disease

Dosage:

Initial dose is 40mg/day (10mg 4 times daily). Maintain this dose for a minimum of 6 weeks with weekly monitoring of transaminase.

Overdosage-

Symptoms Treatment Severe nausea, vomiting, salivation, sweating, bradycardia,

1. Urilize general suportive measures hypotension,collapse and convulsions. Increasing muscle

2. Tertiary anticholinergics such as atropine may be weakness is a possibility and may result in death if respiratory used as an antidote for tacrine overdosage. muscles are involved.

3. IV atropine sulfate titrated to effect is recommended (initial dose of 1 to 2 mg IV with subsequent doses based on clinical response)

4. Atypical increases in blood pressure and heart rate have been reported with cholinomimetics when co-administered with quaternary anticholinergics such as glycopyrrolate

5. It not known whether tacrine or its metabolite can be eliminated by dialysis (hemodialysis) peritoneal dialysis or hemofiltration.

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.

TACRINE HCL - 

1. Advise patients and caregivers the effect of tacrine therapy is thought to depend on its administration at regular intervals as directed. Take between meals whenever possible, however it may be taken with meals to avoid GI upset

2. Advise patients about the possibility of adverse effects.eg nausea, vomiting, loose stools, diarrhea.

3. Advise patients that abrupt discontinuation or a large reduction in total daily dose may cause decline in cognitive function and behavoirial disturbances.

4. 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.

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

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

7. Children -Not reported

8. 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

9. 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

10. 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

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:

Tacrine is centrally acting reversible cholinesterase inhibitor, commonly refered to as THA. Tacrine presumably acts by elevating acetycholine concentrations innthe cerbral cortex by slowing the degradation of acetylaholine released by still intact cholinergic neurons.

Pharmacokinetics:

Tacrine is rapidly absorbed after oral administration. Maximal plasma concentration occur within 1 to 2 hours. Absolute bioavailability of tacrine is about 17%. Food reduces tacrine bioavailability by about 30% to 40 %, however food has no effect if tacrine is administered at least 1 hour before meals.

Food has no effect if the drug is administered 1 hour before meals.

Pregnancy:

Not known if tacrine can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.

Lactation:

It is not known whether tacrine is excreted in breast milk.

Children:

No adequate and well controlled studies and documents available on safety and efficacy on children