Dosing and uses of Valturna (aliskiren-valsartan)
Adult dosage forms and strengths
aliskiren/valsartan
tablet
- 150/160mg
- 300/320mg
Hypertension
Add-on OR initial treatment: aliskiren/valsartan 150/160 mg PO qDay
Maintenance: If needed, may increase after 2-4 weeks to maximum of 300/320 mg PO qDay
Majority of effect attained within 2 weeks
Pediatric dosage forms and strengths
Safety and efficacy not established
Valturna (aliskiren-valsartan) adverse (side) effects
1-10%
Cough (1.1%)
Diarrhea (2.3%)
Rash (1%)
Dizziness (1.4%)
Fatigue (2.6%)
Hyperkalemia (4%)
Hypotension (5.5%)
Nasopharyngitis (2.6%)
Upper RTI (1.4%)
UTI (1.4%)
Vertigo (1.1%)
<1%
Angioedema
Gout
Headache
Renal stones
Postmarketing Reports
Peripheral edema
Increased serum creatinine
Stevens Johnson syndrome
Toxic epidermal necrolysis
Warnings
Black Box Warning
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to aliskiren or valsartan
Pregnancy (2nd and 3rd trimesters): significant risk of fetal and neonatal morbidity and mortality
Use in patients with diabetes
Do not coadminister aliskiren with ARBs or ACEIs in patients with diabetes
Cautions
Caution in volume- or salt-depleted patients
Diabetes mellitus
Severe renal impairment
Monitor renal function periodically
Renal artery stenosis
Hepatic impairment
Monitor for hypotension
Reports of aliskiren-associated head/neck angioedema
Cyclosporine or itraconazole increase aliskiren levels; avoid concomitant use
Coadministration with NSAIDs increase risk for renal impairment; monitor renal function periodically
Coadministration of aliskiren with ACE inhibitors or ARBs
- Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
- When aliskiren was prescribed with ACE inhibitors or angiotensin receptor blockers (ARBs) in the ALTITUDE study, an increased incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension was observed after 18-24 months
- The ALTITUDE trial included patients with hypertension plus type 2 diabetes and renal impairment who were at high risk of cardiovascular and renal events
- FDA notified healthcare professionals of possible risks when using aliskiren with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes or kidney (renal) impairment. Their use is contraindicated in patients with diabetes. Avoid use of aliskiren with ARBs or ACEIs in moderate to severe renal impairment (i.e., where glomerular filtration rate [GFR] < 60 mL/min)
- Hyperkalemia: Increases in serum potassium >5.5 mEq/L were infrequent with aliskiren (0.9% compared to 0.6% with placebo); however, when used in combination with an ACE inhibitor in a diabetic population, increases in serum potassium were more frequent (5.5%)
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd & 3rd trimesters)
Lactation: discontinue drug or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Valturna (aliskiren-valsartan)
Mechanism of action
Aliskiren: Renin inhibitor
Valsartan: Blocks binding of angiotensin II to type 1 angiotensin II receptors
Absorption
Bioavailability: (aliskiren) 2.5%; (valsartan) 25%
Peak Response: (valsartan) 4-6 hr
Peak Plasma Time: (valsartan) 2-4 hr; (aliskiren) 1-3 hr
Onset: (valsartan) 2 hr
Duration: (valsartan) single dose: 6-8 hr, multiple dose: 24 hr
Distribution
Protein Bound: (valsartan) 94-95%
Vd: (valsartan) 17 L
Metabolism
Valsartan metabolized minimally in liver; aliskiren metabolized by CYP3A4
Metabolites: (valsartan) valeryl-4-hydroxyvalsartan (inactive)
Elimination
Half-Life: (valsartan) 6-9 hr; (aliskiren) 24 hr
Total body clearance: (valsartan) 2.2 L/hr
Total renal clearance: (valsartan) 0.62 L/hr
Excretion: (valsartan) feces 83% (89% in bile), urine 7-13%; (aliskiren) urine
