Drug interactions- summary-

+ Eltrombopag-
CYP1A2 inhibitors eg. ciprofloxacin , fluvoxamine / CYP2C8 inhibitors eg gemifibrozil, trimethoprim-
in vivo studies demonostrate that CYP1A2  and CYP2C8   are involved in the oxidative metabolism
of eltrombopag. Monitor patients for signs and symptoms of excessive eltrombopag exposure
when etlrombopagag is coadministered with these moderate or strong inhibitors of CYP1A2 or CYP2CB

Polyvalent cations eg aluminium , calcium, selenium, zinc-
eltrombopag chelates polyvalent cations in foods,mineral supplements, and antacids.
Coadministration of eltrobopag with am antacid (eg aluminium  hydroxide, magnesium carbonate,
sodium alginate) decreased plasma eltrombopag systemic exposure by 70% .
Eltrombopag must be taken 4 hours of any medication containing polyvalent cations 

Eltrombopag +
acetoaminophen, narcotics, non-steroidal antiinflammatory drugs -
monitor closely for signs of excessive exposure to these drugs when coadministrated with
eltrombopag

OATP1B1 substrates eg atrovastain, benzylpenicillin , fluvastatin, methotexate , netglinide,
pravastatin, repaglinide , rifampicin, rosuvastatin )
eltrombopag is an inhibitor of organic anion transporting polypeptide OATP1B1  and can increase
systemic exposure of other drugs that are substrate of the transporter.Use caution  with
coadministration. Monitor patients closely for signs and symptoms of excessive exposure to
the  drugs that are substrates of OAT1B1  and consider reduction of dose of these drugs. 

Thrombocytopenia

Adverse drugs-

 GI -                                       dyspepsia  2%          nausea 6%     vomiting  4%

Hematogical/lymphatic -        echymosis  2%       thrombocytopenia      2%

Hepatic-                             increased  ALT   2%    increased AST   2%

Special senses-               cataract  3%         conjuntivial hemorrhage  2%

Miscellaneous-                 monorrhogia    4%   myalgia  3%    paresthesia  3%

Special precautions-

Hepatotoxicity-     etrombopag administration may cause hepatotoxicity. If liver tests abnormalites
persist, worsen or recur, then permanently discontinue eltrombopag

Bone marrow reticulum formation/bone marrow fibrosis- prior to initiation of eltrombopag examine
a baseline level of cellular morphologic abnormalites.. If the patient develops new or worsening
morphological abnormalites or cytopenias, discontinue treatment with eltrombopag and consider
a bone marrow biopsy,including staining for fibrosis

Discontinuation - discontinuation of eltrombopag may result in thrombocytopenia of greater severity
than was present prior to therapy with eltrombopag. The worsening thrombocytopenia may increase
the patients risk of bleeding, particularly is discontinued while the patient is on anticoagulants or
antiplatelet  agents.

Following discontinuation,obtain weekly CBCs including platelet counts for at least 4 weeks and
consider alternative treatments for worsening thrombocytopenia, according to current treatment to
cuurent treatment guidelines

Thrombobotic/thromboembolic complications- use caution  when administering eltrombopag to
patients with a known risk of thromboembolism. To minimise the risks of thrombotic/thromboembolic
complications do not use eltrombopag in an attempt to normalize platelet counts.

Malignancies- eltrombopag  is not indicated for the treatment of thrombocytopenia due to causes
of thrombocytopenia

Cataracts- Perform a baseline ocular examinations prior to administraton of eltrombopag and
during therapy with eltrombopag, regularly monitor for signs and symptoms of cataracts.

Renal function impairment- the safety snd efficacy of eltrombopag in patients with varying degrees
of renal functin have not been established. losely monitor patients when adminstering the drug

Hepatic function impairment- excecise caution while adminstering eltrombopag to patients with
hepatic disease. for patients moderat to severe hepatic impairment, initiate eltrombopag
dosage of 25mg once daily

Pregnancy- use during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

Lactation-decide whether to discontinue breast feeding or the the drug  depending on the
importance of the drug to the mother.

Children- the safety andefficacy in children have not been  established

Elderly- be cautious in dose adjustment for an elderly patient reflecting the greater frequency
of decreased hepatic, renal or cardiac functions, and of concomittant use of other drug therapy

Monitoring- Monitor CBC including platelet counts and peripheral blood smears prior to initiation,
throughout  and following discontinuation of therapy with eltrombopag

Thrombocytopenia

Dosage-

Maximum dose 75mg tabs daily

Use the lowest dose of eltrombopag to acheive and maintain a platelet count of at least 50 * 10 9/L
as necessary to reduce risk of bleeding

Initial dose- 50mg once daily. Dosage adjustnents are based upon the platelet count  response.

Do not administer more than  1 dose of eltrombopag within 24 hour period 

 Inform patients the following risks and considration for eletrombopag-
 1.  Eltrombopag is not used to normalize platelet counts
  
 2. Therapy with eltrombopag may be associated with hepatobiliary laboratory abnormalities.
    Monitor serum liver tests- ALT, AST and bilirubin

 3.Advice patients to report any of  the followings signs and symptoms of liver problems to their
   health care provider- yellowing of the skin or the whites of the eyes ( jaundice) ,unusual
   darkening of the urine, unusual tiredness, right upper stiomach area pain.

4. Following discontiuation of eltronbopag , thromboctopenia and risk of bleeding may develop
   that is worse than experienced prior to therapy with the drug, particularly if the eletrombopag is
   discontinued while on anticoagulants or antiplatelet agents.

5. Too much eltrombopag may result in excessive platelet counts and risk of thrombotic/
   thromboembolic complications

6. Eltrombopag stimulates bone marrow cells to make platelets and may increase the risk of
    progression of underlying myledysplastic dromes or hematological malignancies

Pregnancy-
Use during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

Lactation-
Decide whether to discontinue breast feeding or the the drug  depending on the
importance of the drug to the mother.

Children-
The safety andefficacy in children have not been  established

Elderly-
Be cautious in dose adjustment for an elderly patient reflecting the greater frequency
of decreased hepatic, renal or cardiac functions, and of concomittant use of other drug therapy