Co-Diovan160 mg+12.5 mg

Co-Diovan is a fixed-dose combination antihypertensive (an angiotensin receptor blocker plus a thiazide diuretic) indicated for:

• Hypertension: Treatment of high blood pressure in adult patients whose blood pressure is not adequately controlled on monotherapy with either component alone. Co-Diovan is also indicated as initial therapy in patients likely to need multiple drugs to reach their blood pressure goal.

Co-Diovan is not indicated for the initial treatment of hypertension in patients who are volume-depleted, nor as a substitute for the individual components when initiating therapy. It lowers blood pressure but has not been specifically studied to demonstrate reduction of cardiovascular morbidity or mortality; benefit is inferred from blood pressure lowering. Use should be individualized by a physician based on response to and tolerability of the individual components.

Each tablet of Valsartan + Hydrochlorothiazide contains valsartan, an angiotensin II receptor blocker (ARB), combined with hydrochlorothiazide, a thiazide diuretic, in fixed-dose strengths such as 80 mg/12.5 mg, 160 mg/12.5 mg, and 160 mg/25 mg, depending on the manufacturer's formulation. Exact strength combinations vary by brand; refer to the specific product label for the strength dispensed.

Co-Diovan is a fixed-dose combination oral tablet that brings together an angiotensin II receptor blocker (valsartan) and a thiazide-type diuretic (hydrochlorothiazide) in a single dosage form for the management of hypertension. Valsartan blocks the vasoconstrictive and aldosterone-secreting effects of angiotensin II, while hydrochlorothiazide promotes renal sodium and water excretion, reducing plasma volume. Combining agents from these two complementary classes typically produces greater blood pressure reduction than either component alone, and the diuretic component can also blunt the compensatory fluid retention sometimes seen with ARB monotherapy. Co-Diovan is taken once daily and is intended for long-term management of hypertension under regular medical supervision.

Co-Diovan belongs to the therapeutic class of combination antihypertensive agents, specifically an angiotensin II receptor blocker (ARB) combined with a thiazide diuretic. It is classified under fixed-dose combination antihypertensives used for the management of essential hypertension.

Valsartan + Hydrochlorothiazide combines two agents with complementary but distinct mechanisms of blood pressure lowering.

Valsartan component

Valsartan is a selective antagonist of the angiotensin II type 1 (AT1) receptor. By blocking AT1 receptors, valsartan prevents the vasoconstriction, aldosterone release, and sympathetic activation normally triggered by angiotensin II, resulting in vasodilation and reduced blood pressure without significantly affecting heart rate. Unlike ACE inhibitors, valsartan does not inhibit kininase II, so it does not typically cause a dry cough related to bradykinin accumulation.

Hydrochlorothiazide component

Hydrochlorothiazide is a thiazide diuretic that acts on the distal convoluted tubule of the nephron, inhibiting the sodium-chloride symporter and thereby increasing excretion of sodium, chloride, and water while increasing potassium and magnesium loss. The resulting reduction in plasma volume contributes to blood pressure lowering; with chronic use, a component of peripheral vasodilation also contributes to the antihypertensive effect. The diuresis from hydrochlorothiazide activates the renin-angiotensin-aldosterone system, and the valsartan component blunts this compensatory response, giving the combination synergistic antihypertensive activity.

Pharmacokinetically, valsartan reaches peak plasma concentration in about 2-4 hours with an elimination half-life of approximately 6 hours and is largely eliminated unchanged in bile/feces, while hydrochlorothiazide reaches peak plasma concentration in 1-2 hours with a half-life of 6-15 hours and is eliminated primarily unchanged by the kidney.

Co-Diovan is taken orally, once daily, at approximately the same time each day, with or without food. The tablet should be swallowed whole with a glass of water and should not be crushed or chewed unless a physician or pharmacist specifically advises otherwise. Blood pressure should be monitored regularly while taking Co-Diovan, and adequate hydration should be maintained unless a physician advises fluid restriction.

Co-Diovan has clinically significant interactions with the following:

• Potassium-sparing diuretics, potassium supplements, and salt substitutes containing potassium: The valsartan component can increase serum potassium; concomitant use may result in hyperkalemia and requires monitoring of serum potassium.
• Lithium: Both ARBs and thiazide diuretics reduce renal lithium clearance, increasing serum lithium levels and the risk of lithium toxicity; concomitant use with Co-Diovan requires frequent monitoring of lithium levels.
• NSAIDs (including selective COX-2 inhibitors): May reduce the antihypertensive effect of both components and can further deteriorate renal function, particularly in volume-depleted patients; monitor renal function and blood pressure.
• Aliskiren: Concomitant use of Co-Diovan with aliskiren is contraindicated in patients with diabetes due to increased risk of hyperkalemia, hypotension, and renal impairment (see Contraindications).
• Other antihypertensives and diuretics: May produce additive blood-pressure-lowering effects, increasing risk of symptomatic hypotension, particularly after the first dose.
• Digoxin: Hydrochlorothiazide-induced hypokalemia or hypomagnesemia can increase the risk of digoxin toxicity; electrolytes should be monitored.
• Corticosteroids/ACTH: May intensify electrolyte depletion, particularly hypokalemia, caused by the hydrochlorothiazide component.
• Cholestyramine/colestipol resins: May reduce absorption of the hydrochlorothiazide component; administer at a different time.

Always inform the physician or pharmacist of all other medicines being taken before starting Co-Diovan.

Side effects of Co-Diovan arise from its two components.

Common

• Dizziness or light-headedness
• Headache
• Fatigue
• Upper respiratory tract symptoms
• Diarrhea
• Mild hypotension, especially after the first few doses

Less Common/Serious

• Electrolyte disturbances: hypokalemia, hyponatremia, and, less commonly, hyperkalemia (net effect requires monitoring - see Precautions and Warnings)
• Hyperuricemia and precipitation of gout
• Hyperglycemia and worsening of glycemic control in diabetic patients (thiazide-related)
• Symptomatic hypotension, particularly in volume- or salt-depleted patients
• Deterioration of renal function, particularly with pre-existing renal impairment or volume depletion
• Photosensitivity reactions (thiazide-related)
• Angioedema (rare)

Patients should seek prompt medical advice for severe dizziness, fainting, muscle cramps or weakness, palpitations, marked reduction in urination, or swelling of the face/lips/tongue while taking Co-Diovan.

Pregnancy - Boxed Warning: Fetal Toxicity

Co-Diovan can cause fetal harm and even death when administered to a pregnant woman, because drugs that act directly on the renin-angiotensin system (such as the valsartan component) can cause injury and death to the developing fetus, including oligohydramnios, fetal growth restriction, renal failure, skull hypoplasia, and death, particularly when used in the second and third trimesters. Co-Diovan is contraindicated in pregnancy; it should be discontinued as soon as possible once pregnancy is detected, and an alternative antihypertensive should be selected by the physician for ongoing management.

Lactation

It is not known whether valsartan is excreted in human milk; hydrochlorothiazide is excreted in breast milk in small amounts. Because of the potential for adverse effects in a nursing infant, a decision should be made by the physician whether to discontinue breastfeeding or discontinue Co-Diovan, taking into account the importance of the drug to the mother.

Fetal toxicity: See the boxed warning under Pregnancy and Lactation - Co-Diovan must be discontinued as soon as pregnancy is detected.

Hypotension in volume- or salt-depleted patients: Symptomatic hypotension may occur after the first dose in patients who are volume- or salt-depleted (e.g., from prior diuretic therapy, dietary salt restriction, vomiting, or diarrhea); correct volume/salt depletion before starting Co-Diovan, or begin under close medical supervision.

Renal function: As with other agents affecting the renin-angiotensin system, deterioration of renal function may occur, particularly in patients whose renal function depends on the renin-angiotensin-aldosterone system (e.g., severe heart failure or renal artery stenosis). Co-Diovan is not recommended in severe renal impairment and is contraindicated in anuria.

Electrolyte imbalance: Periodic monitoring of serum electrolytes is recommended to detect hypokalemia, hyponatremia, or hyperkalemia; the net effect on potassium varies because hydrochlorothiazide wastes potassium while valsartan can raise it.

Hyperuricemia/gout: The thiazide component may raise serum uric acid and precipitate attacks of gout in susceptible individuals.

Diabetes/glycemic control: Thiazides may alter glucose tolerance and raise blood glucose; monitor glycemic control in diabetic patients on Co-Diovan.

Sulfonamide allergy: Hydrochlorothiazide is a sulfonamide-derived drug; patients with a history of allergy to sulfonamide drugs may show cross-reactivity and should be monitored for hypersensitivity reactions.

Hepatic impairment: Use with caution, as minor fluid and electrolyte alterations from the hydrochlorothiazide component may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

Lupus erythematosus: Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Driving/operating machinery: Co-Diovan may cause dizziness, especially after the first dose; caution is advised when driving or operating machinery.

Overdose with Co-Diovan is most likely to cause pronounced hypotension and dizziness from the valsartan component, and electrolyte depletion (hypokalemia, hyponatremia) with dehydration from the hydrochlorothiazide component; bradycardia or tachycardia may also occur. Any suspected overdose of Co-Diovan is a medical emergency - seek immediate medical attention or contact a poison control center/emergency services right away. Management must be carried out under medical supervision, typically with supportive care, monitoring of vital signs and electrolytes, and correction of fluid/electrolyte imbalance; do not attempt to treat an overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly

No overall dose adjustment is generally required in elderly patients, but they may be more sensitive to the blood-pressure-lowering effects of Co-Diovan; start at the lowest appropriate dose and titrate slowly.

Renal Impairment

Not recommended in severe renal impairment; contraindicated in anuria. See Dosage and Administration.

Hepatic Impairment

Use with caution; see Precautions and Warnings and Dosage and Administration.

Pediatric

Not recommended as a fixed-dose combination; safety and efficacy not established (see Pediatric Uses).

Pregnancy and Lactation

Contraindicated in pregnancy (fetal toxicity); see Pregnancy and Lactation section for full details.

Co-Diovan is generally used long-term, often for months to years, as part of ongoing management of chronic hypertension. It should be continued for as long as the treating physician advises, with periodic review of blood pressure control, renal function, and electrolytes.

Angiotensin II receptor blocker (valsartan) combined with a thiazide diuretic (hydrochlorothiazide); combination antihypertensive.

Valsartan + Hydrochlorothiazide lowers blood pressure through two complementary mechanisms: valsartan selectively blocks the angiotensin II type 1 (AT1) receptor, preventing angiotensin II-mediated vasoconstriction and aldosterone release, while hydrochlorothiazide inhibits sodium-chloride reabsorption in the distal convoluted tubule, increasing sodium and water excretion and reducing plasma volume. The diuresis-induced activation of the renin-angiotensin system is blunted by the concurrent AT1 blockade, producing an antihypertensive effect greater than either component alone.

D

The safety and efficacy of Co-Diovan as a fixed-dose combination have not been established in pediatric patients. Use in children and adolescents is not recommended. Hypertension in children, when present, should be evaluated and managed by a pediatric specialist using age-appropriate, individually titrated therapy rather than fixed-dose adult combination products such as Co-Diovan.