Interacting drugs- summary

Raloxifene + Ampicillin

 Ampicillin reduces peak concentration and absorption

Cholestyramine 

Cholestyramine reduces absorption and enterohepatic recycling of raloxifene

Warfarin 

Coadministration of raloxifene with warfarin reduces the prothrombin response and time

Digoxin

Raloxifene has no effect on the pharmacokinetics of Digoxin 

Postmenopausal osteoporosis 

       Patent Expiry Date of drugs (Ref - IDMA Publication)   

Hot flushes , leg cramps, sweating , sleeping disorders, peripheral oedema, vaginal bleeding, endometrial carcinoma and thromboembolic events.

Pregnancy and lactation, hypersensitivity to drug, history of thromboembolic events, hepatic insufficiency.

Special Precautions:

Plasma concentrations of raloxifene is elevated in patients with hepatic insufficiency.

Use with caution Concomittant use of Raloxifene with systemic estrogen not recommended. To be used with in patients taking highly protein bound drugs viz. diazepam, diazoxide, and lidocaine. In patients taking warfarin or other coumarinderivatives, prothrombin time should be closely monitored, when starting or stopping raloxifene.

 Indications

Postmenopausal osteoporosis.

Dosage-

Oral dose- 60mg/day may be administered without respect to meal times.

Overdose-

Incidents of over dose in humans have not been reported. No specific antidote for raloxifene

Pharmacology:

Raloxifene has agonistic effects at some estrogen receptors, antagonistic effects at other estrogen receptors. Raloxifene influences gene transcription, via the intermediation of the estrogen receptor, by interacting with a DNA site .

This molecular target has been called as the raloxifene response element(RRE) Transforming growth factor (TGF)- Beta 3 is an important regulator of bone remodelling. Raloxifene activates the gene encoding transforming growth factor beta (TGF- Beta3) which together with other cytokines induces production of osteoblasts and inhibits the activity and shortens the life span of osteoclasts.

Pharmacokinetics:

Raloxifene is absorbed rapidly after oral administration. Approximately 60% of the drug is absorbed from the the gastrointestinal tract. The drug undergoes extensive first pass glucoronidation and unchanged drug accounts for 1% of circulating concentrations. Raaloxifene is more than 95% bound to human absolute bioavailability of 2% . The plasma elimination half-life of raloxifene is 27.7 hours. Drug excretion is predominantly via the faecal route and occurs within 5 days of administration. About 5% of the administered dose is excreted in urine as glucoronide conjugates.

The drug may be administered without respect to meal times.

Not recommended during pregnancy and lactation.

Use in Men- Safety and efficacy of Raloxifene have not been evaluated in men.

Use in Elderly- The pharmacokinetic disposition of raloxifene is similar aming young adults and the elderly. In various clinical trials safety and efficacy in older and younger postmenopausal women in osteoporosis treatment trial appeared to be comparable.

Use in Children- Raloxefene should not be used in children.