Interactions -Summary

+ Aliskiren

 Atorvastatin + Aliskiren    -   co-admin increases activity

Irbesaran + Aliskiren   -   co-admin decreases activity

Ketoconazole + Aliskien  -   co-admin increases activity

Aliskiren + Furosemide  -   activity decreased

Furosemide   -   co-administration decreases furosemide AUC and Cmax 30% and 50% respy.

Angioedema- Two cases with angioedema with respiratory symptoms were reported with Aliskiren use in clinical studies Two other cases of periorbital edema without respiratory symptoms were reported as possible angioedema and resulted in discontinuation

Cough-, Aliskerin was associated with a slight increase in cough in placebo-controlled studies

Discontinuation- Aliskerin has been evaluated for safety in patients for periods longer than 6 months, and also on patients for longer than 1 year. In placebo-controlled clinical trials, discontinuation of therapy because of clinical adverse reactions including uncontrolled hypertension occured in 2.2% of treated patients with aliskerin versus 3.5% of patients given placebo

GI- Aliskerin produces dose-related GI adverse reactions. diarrhea was reported in  patients.

In women and elderly, (65 years of age and older ) patients, increases in diarrhea was evident starting at dosage of 150mg daily

Other GI symptoms- abdominal pain, dyspepsia, and gastro-esphageal reflux . Diarrhea and other GI symptoms were typically mild and rarely led to discontinuation.

Other Adverse reactions-

Rash  < 0.5%    Elevated uric acid  0.4%  Gout  0.2 %  Renal stones  0.2%

Lab test abnormalites- Creatinine kinase- increase in kinase of more than 300% in about more than 1% of aliskiren monotherapy patients.

Haemoglobin and hematocrit - small decrease in hemoglobin and hematocrit

Potassium- increase in serum potassium greater than 5.5mEq/L were infrequent in patients with esstential hypertension BUN , creatinine-

Minor increase in BUN or creatinine were observed in less than 7% of patients

Serum uric acid- aliskiren monotherapy produced small increase in serum uric acid levels.

None known

Special precautions-

Head and neck angioedema- Angioedema of the face, extremities, lips, tongue, glottis, and or larynx reported. This may occur at any time during treatment

Hypotension-

In patients with activated renin angiotensin system, such as volume or salt depleted patients (eg. those receiving high dose of diuretics) symptomatic hypotension could occur after initiating treatment with aliskiren.

Correct this condition prior to administration of aliskirten or start the treatment under medical supervision

Hyperkalemia-

When used in combination with ACE inhibitors, in a diabetic population, increase in serum potassium are more frequent 

Routine monitoring of electrolytes and renal function is indicated in this population.

Renal function impairment- Excercise caution in patients with impaired renal function

Pregnancy

Category C (first trimester ) Category D - ( second and third trimester) No clinical experience with use of aliskiren in pregnant women

Lactation-

Due to potential for adverse rections on the breast feeding infant, decide to use or not based on importance of the drug to the mother

Children- Safety for use not established

Indication

Hypertension

Dosage-

Intial dose- 150mg once daily Daily dose may be increased to 300mg

Doses above 300mg did not give an increased blood pressure response, but increased the rate of diarrhea

Can be given concomittantly with other antihypertensive agents

1. Advice women of childbearing age about the the consequences of second and third trimester exposure to drugs that act on renin-angiotensin system

2. Ask these patients to report pregnancy to the doctor as soon as possible

3. Advice patients that angioedema, including laryngeal edema may occur at any time during the treatment with Asikerin

4. Patients should report any signs or symptoms suggesting angioema ( e.g. swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing, or breathing )

5.Patient should not take any more of the drug until they have consulted their doctor

Pharmacology-

Aliskerin is a direct renin inhibitor, decreasing plasm renin activity PRA and inhibiting the conversion of angiotensin I.

Pharmacokinetics-

Aliskerin is poorly absorbed ( bioavailability about 2.5% ) drug with an approximate accumulation half-life of 24 hours Steady state blood levels are reached in about 7 to 8 days Folowing oral administratin, peak plasma levels are reached within 1 to 3 hours. When taken with a hiugh fat meal, mean area under curve AUC and maximum drug concentration Cmax are decreased 71% and 85% respy.

When taken with a high fat meal, AUC and max of the drug are decreased 71% and 85% respy.

Pregnancy

Category C (first trimester ) Category D - ( second and third trimester) No clinical experience with use of aliskiren in pregnant women

Lactation-

Because of potential for adverse rections on the breast feeding infant, decide to use or not based on importance to the mother

Children-

Safety for use not established