TEKAMLO
Clinical safety rating
cautionComprehensive clinical and safety monograph for TEKAMLO (TEKAMLO).
Combination of aliskiren (direct renin inhibitor) and amlodipine (dihydropyridine calcium channel blocker). Aliskiren inhibits renin, reducing angiotensin I and II formation; amlodipine inhibits calcium ion influx across cardiac and vascular smooth muscle, causing vasodilation.
| Metabolism | Aliskiren: minimal metabolism via CYP3A4; amlodipine: extensively metabolized by CYP3A4 |
| Excretion | TEKAMLO (amlodipine/valsartan) excretion: amlodipine is extensively metabolized in the liver with 60% of metabolites excreted renally and 20-25% via feces; unchanged drug in urine <10%. Valsartan is primarily excreted unchanged in feces (70-80%) via biliary elimination, and 13% in urine as unchanged drug. |
| Half-life | Amlodipine terminal half-life: 30-50 hours (mean 35 hours), allowing once-daily dosing; steady-state achieved after 7-8 days. Valsartan terminal half-life: ~6 hours, but pharmacodynamic effect persists due to tight AT1 receptor binding. |
| Protein binding | Amlodipine: ~97.5% bound to plasma proteins (albumin). Valsartan: 94-97% bound to serum proteins (mainly albumin). |
| Volume of Distribution | Amlodipine Vd: ~21 L/kg, indicating extensive extravascular distribution. Valsartan Vd: ~5-10 L/kg, indicating moderate distribution into tissues. |
| Bioavailability | Amlodipine: oral bioavailability 64-90% (mean ~64%). Valsartan: oral bioavailability ~23% (range 10-35%). Both are administered orally only. |
| Onset of Action | Amlodipine: gradual onset, with initial antihypertensive effect within 2-6 hours; maximal effect at 6-12 hours. Valsartan: onset within 2 hours; peak effect at 4-6 hours after oral administration. |
| Duration of Action | Amlodipine: duration >24 hours due to long half-life, effective for once-daily dosing. Valsartan: duration 24 hours despite shorter half-life, due to sustained receptor blockade. |
| Molecular Weight | 558.66 Da (olmésartan medoxomil: 558.66 Da; amlodipine: 408.88 Da as amlodipine besylate) |
One tablet (40 mg telmisartan/5 mg amlodipine) orally once daily; maximum dose: 80 mg telmisartan/10 mg amlodipine per day.
| Dosage form | TABLET |
| Renal impairment | No adjustment for GFR ≥30 mL/min. Contraindicated if GFR <30 mL/min due to telmisartan component. Amlodipine not dialyzable. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Use lowest available strength, titrate slowly; avoid if severe impairment. |
| Pediatric use | Safety and efficacy not established in patients <18 years. |
| Geriatric use | Start at lowest available strength (40/5 mg); titrate slowly due to increased risk of hypotension and renal impairment. |
| 1st trimester | Contraindicated due to risk of fetal hypotension, oligohydramnios, and renal impairment. Angiotensin II receptor blockers (olmesartan component) are associated with adverse fetal outcomes in the first trimester. |
| 2nd trimester | Contraindicated due to risk of fetal hypotension, oligohydramnios, and renal impairment. Second trimester exposure is associated with oligohydramnios and fetal lung hypoplasia. |
| 3rd trimester | Contraindicated due to risk of fetal hypotension, oligohydramnios, and renal impairment. Third trimester exposure is associated with neonatal renal failure, skull hypoplasia, and death. |
Clinical note
Comprehensive clinical and safety monograph for TEKAMLO (TEKAMLO).
| Placental transfer | Both olmesartan and amlodipine cross the placenta. Olmesartan exhibits significant placental transfer with fetal-to-maternal concentration ratios of approximately 0.5-0.9 in animal studies. Amlodipine crosses the placenta but to a lesser extent. |
| Breastfeeding | Olmesartan is excreted into breast milk in minimal amounts; amlodipine is excreted in low concentrations. Use with caution in nursing mothers, especially when breastfeeding premature infants or those with renal impairment. Monitor infant for hypotension and renal function. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Fetal toxicities (oligohydramnios, renal dysfunction, skull ossification delay) with angiotensin II receptor blocker (ARB) class. Second/third trimester: Oligohydramnios, fetal renal failure, hypotension, hyperkalemia, skull hypoplasia; risk is highest in second and third trimesters. |
| Fetal Monitoring | Monitor maternal blood pressure, serum creatinine, potassium, and urine output. Fetal ultrasound to assess amniotic fluid volume and renal function; serial growth scans. |
| Fertility Effects | No specific human data; animal studies show no impairment of fertility with amlodipine or telmisartan at therapeutic doses. |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyHypersensitivity to olmesartan medoxomil, amlodipine, or any component of the formulationConcomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m²)
| Precautions | Risk of hypotension/syncope in volume-depleted patients, Avoid use in pregnancy (potential fetal harm), Monitor renal function and electrolytes, especially in patients with renal artery stenosis, Peripheral edema (more common in women, dose-dependent) |
| Food/Dietary | Avoid grapefruit and grapefruit juice; they inhibit CYP3A4 metabolism of amlodipine, increasing risk of toxicity. Limit high-potassium foods (e.g., bananas, oranges, leafy greens, salt substitutes) due to aliskiren's potential to raise serum potassium. Maintain adequate hydration but avoid excessive sodium intake. No significant interaction with alcohol but advised to limit consumption. |
| Clinical Pearls | Tekamlo is a fixed-dose combination of aliskiren and amlodipine. Monitor renal function and electrolytes due to aliskiren's renin inhibition; avoid in severe renal impairment (eGFR <30 mL/min). Amlodipine may cause peripheral edema, especially at higher doses. Gradual titration reduces edema risk. Do not use aliskiren with ACE inhibitors or ARBs in patients with diabetes or renal impairment (eGFR <60 mL/min). |
| Patient Advice | Take this medication exactly as prescribed, usually once daily. · Do not use with other blood pressure medications unless directed by your doctor. · Avoid grapefruit and grapefruit juice as they can increase amlodipine levels and side effects. · Report signs of edema (swelling in ankles/feet), dizziness, or fainting. · Do not take if you are pregnant or planning to become pregnant; stop immediately if pregnant. · Do not use salt substitutes containing potassium without consulting your doctor. · Stay hydrated, but avoid excessive intake of potassium-rich foods (bananas, oranges, spinach). · Do not stop abruptly without medical advice; monitor blood pressure regularly. |
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