Drug interactions- summary

Strong CYP2C19 inhibitors eg omeprazole + Ambristeran-
use caution when ambrisetran is administered with strong CYP2C19 inhibitors. Thes agents
may cause increased exposure to ambrisetran

Strong  CYP3A inhibtors ( cyclosporine, ketoconazole) + Ambristeran-
use caution when ambisetran is coadministered with strong CYP3A4 inhibitors.
These agents may cause increased exosure to ambrisetran

Pulmonary arterial hypertension

Adverse reactions-

GI -       abdominal pain 1%     constipation 2%

Respiratory -     dyspnea 3%    nasal congestion 2%    nasopharyngitis 2%
                           palpitations   2%

Miscellaneous-      flushing 1%    headache 14%     peripheral edema   11%

In women who are or may become pregnant

Special Precautions-
Hepatic effects- ambisetran can cause elevation of liver aminotransferase ALT and AST
to atleast 3 times the upper limit of normal values.
If aminotransferase elevations of more than 8 times the ULN stop treatment and do not
reinitiate

Hematological effects- decreases in hemoglobin concentration and hemotocrit have followed
administration of other endothelin receptor antagonists were observed with studies with
ambrisentran.
The cause of the decrease in hemoglobin  is unknown , but it does not result in from
hemorhage or hemolysis

Hepatic function impairment- ambristran is not recommended in patients with moderate to
severe hepatic function impairment. Use caution when administering ambrisetran to patients
with mild, preexisiting hepatic function impairment who may require reduces doses of ambrisetran

Pregnancy- adminsetran may cause fetal harm when administered to a pregnant woman
Ambrisetran is contraindicated in women who are ormay become pregnant

Lactation- breast feeding while receiving ambrisetran is not recommended

Children- safety and efficacy of ambrisetran inchildren have not been evaluated

Elderly- peripheral edema was more common in elderly patients than in younger patients

Monitoring- hemoglobin must be measured prior to initiation of therapy and shoould be measured
at 1 month and prodically thereafter

Monitor liver function tests

For women of child bearing potential order and review of pregnancy priorv to initiation of
amrisetran treatment and then at montly during treatment

Indication-

Pulmonary arterial hypertension

Dosage-
Initiate treatment with 5mg once daily with or without food and consider increasing the dose to
10mg once daily if 5mg is tolerated

Women of childbearing potential - treat only after a negative pregnancy test only women who
are using 2 reliable method  of contraception unless the patient has had a tubular sterilization

Pregnancy test should be obtained monthly in women of child bearing potential taking ambrisentan

Hepatic function impairment - Ambrisentan is not recommended in patients with moderate to
severe hepatic  function impairment

1. Advice patients that ambrisetran cause fetal harm.

2. Only initiate Ambrisetran treatment in women of child bearing potential following a negative
    pregnancy test

3. Instruct patients to immediately contact their doctor if they suspect they might be pregnant

4. Advice patients the importance of montly liver function testing and instruct them to immediately
   report any symtoms of potential liver injury such as anorexia, nausea, vomiting , fever, malaise,
   fatigue, right upper quardent abdominal discomfort , jaundice,dark urine, or itching to their doctor

Pregnancy-
Adminsetran may cause fetal harm when administered to a pregnant woman
Ambrisetran is contraindicated in women who are ormay become pregnant

Lactation-
Breast feeding while receiving ambrisetran is not recommended

Children-
Safety and efficacy of ambrisetran inchildren have not been evaluated

Elderly-
Peripheral edema was more common in elderly patients than in younger patients