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. |
| Molecular Weight | 611.8 |
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 | Contraindicated due to risk of fetal nephrotoxicity and oligohydramnios; potential for teratogenic effects based on ACE inhibitor class. |
| 2nd trimester | Contraindicated; may cause fetal renal dysfunction, oligohydramnios, and skull ossification defects. |
| 3rd trimester | Contraindicated; risk of neonatal hypotension, renal failure, and hyperkalemia. |
Clinical note
Comprehensive clinical and safety monograph for VALTURNA (VALTURNA).
| Placental transfer | Crosses placenta; documented in animal studies and human case reports; associated with fetal renin-angiotensin system interference. |
| Breastfeeding | Excreted into human milk in low amounts; potential for serious adverse effects in nursing infants, including hypotension and renal impairment. Not recommended during breastfeeding. |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyHistory of angioedema related to previous ACE inhibitor or ARB therapyConcomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²)Hypersensitivity to any component of the formulation
| 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 |
| Food/Dietary | High-fat meals may reduce absorption of aliskiren; take consistently with or without food. Avoid grapefruit juice as it may increase aliskiren levels. Avoid potassium-rich foods (bananas, oranges, spinach) in large amounts due to risk of hyperkalemia. |
Loading safety data…
| Lactation Rating |
| L5 - Contraindicated |
| 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. |
| 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. |
| Clinical Pearls | Valturna (aliskiren and valsartan) combines a direct renin inhibitor with an ARB. Avoid use in diabetes with ACEi or ARB due to increased risk of renal impairment, hypotension, and hyperkalemia. Monitor renal function and electrolytes 1-2 weeks after initiation. Contraindicated in pregnancy. Do not co-administer with cyclosporine or itraconazole due to strong CYP3A4 inhibition increasing aliskiren levels. |
| Patient Advice | Do not use if pregnant or planning to become pregnant; stop and call your doctor immediately if you become pregnant. · Avoid salt substitutes containing potassium unless approved by your doctor. · May cause dizziness; avoid driving if affected. Rise slowly from sitting or lying positions. · Take once daily at the same time, with or without food. Do not double dose. · Report symptoms of low blood pressure (lightheadedness), high potassium (muscle weakness, slow heart rate), or kidney issues (swelling, fatigue). |