Drug interaction- summary-

+  Lapatinib

Azole antifungal eg. itraconazole, ketoconazole, voriconazole

avoid coadministration. If use cannot be avoided, reduce the lapitinib dosage
to 500mg daily

Barbiturates  eg phenobarbital

avoid coadministrtion. If use cannot be avoided increase  dosage of lapatinib
gradually to 4500 mg/day

Carbamazepine

avoid concomittant use. If use cannot be avoided, increase the lapttinib dosage
gradually to 4500mg daily

Clarithromycin

avoid coadministration. If use cannot be avoided reduce gradually the lapitinab
to 500mg/day

Dexamethasone

avoid coadminiostration. If use cannot be avoided , increase lapatinib dosage
gradually to 4500mg daily

Hydantoin eg fosphenytoin,phenytoin

avoid coadministration, If use cannot be avoided, increase lapatinib dosage
gradually to 4500mg daily

Nefazodone

avoid coadministration. If use cannot be avoided, reduce lapitinib  dosage
 to 500 mg daily

Protease inhibitors eg atazanvir, indinavir, ritonavir, saquinavir

avoid coadministration. If use cannot be avoided,  reduce lapitinab dosage
to 500mg daily

Rifamycin eg rifabutin, rifampin rifapenim

avoid concomittant use. If use cannot be avoided increase lapitinib  dosage
gradually to 4500mg/day

St Johns wart

avoid concomittant use. if use cannot  be avoided increase the lapitinib dosage
gradually to 4500mg/day

Telithromycin

avoid coasdministration. if use cannot be avoided reduce the lapitinib dosage
to 500mg/day

Most common adverse reactions-

GI diarrhea, nausea, and vomiting , dermatologic palmar erythrodysethesia  and rash
and fatigue . Diarrhea was most common reactions.

CNS -  insomina   9%   palmar plantar erythrodysethesia   50%    rash    25%

GI -     diarrhea   60%     dyspesia  10%     stomatitis    12%    vomiting   24%

Musculoskeltal -    back pain   10%   pain in extremity    10%

Respiratory -         dyspnea    10%

Miscellaneous -      mucosal inflammation    12%

Lab test abnormalites- 

Hematologic -        haemoglobin     53%      neutropohils  20%    platelets   15%

Hepatic -               ALT   35%       AST     43%      Total bilirubin   42%  

Not known

Special Precautions/Warnings-

Cardiac effect - decreased left ventricular ejection factor- laptinib has been reported to
decrease LVEF. Continue to evaluate LVEF during treatment with lapitinib to ensure that
 LVEF does not decline below the normal limits.

QT prolongation- administer lapitinib with caution to patients who have or may develop
 prolongation of QTc . These conditions include patients with hypokalemia or hypomaganesemia, congenital long term QT syndrome therapy with antiarrhythmics.

Diarrhea - severe diarrhea may require administration of oral or intravenous IV electrolytes
and fluids and interruption or discontinuation of therapy with lapatinib

Interstitital lung disease/pneumonitis - lapitinib has been associated with interstitial lung
disease and pneumonitis in monotherapy or in combination with other chemotherapies.
Discontinue lapatinib in patients who experience plumonary symtoms indicative of 
interstitial  lung disease or pneumonitis 

Hepatic function impairment - use with caution in patients with patients with severe  hepatic function impairment 

Pregnancy-    Advice women not to become pregnant when taking lapatinib. If the patient
becomes pregnant while taking the drug, appraise the patient of the potential hazard to
the fetus.  

Lactation- decide whether to discontinue breast feeding or the drug depending upon the
importance of the drug to the mother
 
Children-    safety or efficacy of lapatinib in children have not been established.

Monitoring-  evaluate LVEF throughout  use. Consider base line and on treatment-
electrocardiograms ECGs with QT prolongation measurement.
Monitor  pulmonary symptoms indicative of interstitial  disease or pneumonitis

Indication-

Breast cancer

Dosage -
Adults - 1250mg ( 5 tablets ) given orally on days 1 to 21 continuosly in combination with
capecitabine 2000mg/m2/day ( administerd orally in 2 dose approximately 12 hours apart )
on day 1 to 14 a repeating 21 day cycle

Maximum - 1250 mg/day for 4500mg/day in patents taking concomittant  strong CYp3A4
inducers

Storage -  store at 25C ( 77F )

1. Inform patients that lapitinib has been reported to decrerase LVEF  whicn may result in
shortness of breath , palpitations , and or fatigue.  Instruct patients to inform their health
care provider if they develop these symptoms while taking lapintinib.

2. Inform patients that lapitinib often causes diarrhea, which  may be severe in some cases.
Advice them to how they can manage diarrrhea and to inform  their doctor if it becomes
 very severe

3. Lapatinib may interact with many drugs therfore advice patients  to inform  their doctor
about the use of any other prescription medicines or herbal products.

4. inform the patients of the importance of taking lapatinib at least 1 hour before or 1 hour
after a meal , in contrast to capacitabine which should be taken with food or within  30 minutes
after food.

5. Advice patients not to take lapatinib with grape fruit products.

6. Do  not divide the dose of lapatinib , Advice patients of the importance of taking lapatinib
once daily , in contrast to capecitabine which is taken twice daily.

Lapatinib should be tasken at least 1 hour before or 1 hour after a meal , in contrast to
capacitabine which should be taken with food or within  30 minutes after food.

Pregnancy-   
Advice women not to become pregnant when taking lapatinib. If the patient
becomes pregnant while taking the drug, appraise the patient of the potential hazard to
the fetus.  

Lactation-
Decide whether to discontinue breast feeding or the drug depending upon the
importance of the drug to the mother
 
Children-   
Safety or efficacy of lapatinib in children have not been established.