VALTURNA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VALTURNA (VALTURNA).
Valsartan is an angiotensin II receptor blocker (ARB) that selectively inhibits the AT1 receptor, reducing vasoconstriction and aldosterone secretion. Aliskiren is a direct renin inhibitor that decreases renin activity, lowering angiotensin I and II levels.
| Metabolism | Valsartan is primarily metabolized by CYP2C9; aliskiren is minimally metabolized, mainly excreted unchanged via bile and urine. |
| Excretion | Aliskiren: 78-90% of absorbed dose excreted unchanged via biliary/fecal route (hepatic), ~2.2% renal; Valsartan: 83% excreted unchanged in feces via bile, 13% renal. |
| Half-life | Aliskiren: terminal half-life ~24 hours (range 23-28 h), supports once-daily dosing; Valsartan: terminal half-life ~6 hours (range 5-9 h), but clinical effect persists >24 h due to sustained AT1 receptor blockade. |
| Protein binding | Aliskiren: ~47-49% bound to plasma proteins (primarily albumin); Valsartan: 94-97% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Aliskiren: ~135 L (approx 1.7-2.0 L/kg for a 70 kg adult), indicating extensive tissue distribution; Valsartan: ~17 L (approx 0.24 L/kg for a 70 kg adult), consistent with distribution primarily into plasma and interstitial fluid. |
| Bioavailability | Aliskiren: oral bioavailability ~2.5% (low due to first-pass metabolism and efflux); Valsartan: oral bioavailability ~25% (highly variable, decreased by food). Combine as Valturna: overall bioavailability determined by each component; consider food effect reduces valsartan exposure by 40-50%. |
| Onset of Action | Oral: Aliskiren - 2 hours; Valsartan - 2-4 hours; combined effect on blood pressure reduction observed within 1-2 weeks of therapy. |
| Duration of Action | Blood pressure reduction persists for 24 hours with once-daily dosing for both components; steady-state achieved after 5-7 days for aliskiren and within 1-2 weeks for valsartan. |
One capsule orally once daily; dose depends on prior ARB or ACEi therapy: for patients not on an ARB or ACEi, start with 80/5 mg; for patients switching from an ARB, start with 160/5 mg; dose can be titrated to 160/5 mg or 320/10/12.5 mg based on BP response.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with GFR <30 mL/min/1.73 m². For GFR 30-49 mL/min/1.73 m², maximum recommended dose is 160/5 mg once daily. For GFR ≥50 mL/min/1.73 m², no adjustment. |
| Liver impairment | For Child-Pugh class A: no adjustment. For Child-Pugh class B: not recommended. For Child-Pugh class C: contraindicated. |
| Pediatric use | Not recommended for patients <18 years of age due to lack of safety and efficacy data. |
| Geriatric use | In patients ≥65 years, initiate with 80/5 mg once daily; titrate cautiously due to risk of hypotension and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VALTURNA (VALTURNA).
| Breastfeeding | No data on excretion in human milk. Due to potential for adverse effects in the nursing infant, breastfeeding is not recommended. M/P ratio unknown. |
| Teratogenic Risk | First trimester: Drugs acting on the renin-angiotensin system (RAS) can cause fetal renal dysfunction, oligohydramnios, and skull ossification defects. Second and third trimesters: Fetal exposure to RAS inhibitors is associated with oligohydramnios, fetal renal dysplasia, pulmonary hypoplasia, and death. Risk is highest in second and third trimesters. |
■ FDA Black Box Warning
None
| Serious Effects |
["Pregnancy (Category D, risk of fetal injury)","History of angioedema with previous ARB or direct renin inhibitor therapy","Concurrent use with cyclosporine or strong P-glycoprotein inhibitors (e.g., itraconazole) due to aliskiren interaction","Severe renal impairment (eGFR <30 mL/min/1.73 m²)"]
| Precautions | ["Fetal toxicity (discontinue if pregnancy detected)","Hypotension in volume-depleted patients","Renal impairment (monitor renal function)","Hyperkalemia (risk factors: diabetes, renal dysfunction)","Avoid use with ARBs or ACE inhibitors due to increased adverse events"] |
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| Fetal Monitoring |
| Monitor fetal ultrasound for oligohydramnios and renal function. Assess maternal blood pressure and electrolyte status. If oligohydramnios occurs, consider stopping therapy. |
| Fertility Effects | No specific human data. In animal studies, no impairment of fertility was observed. However, RAS inhibitors are generally avoided in women planning pregnancy due to potential fetal harm. |