Co Diovan is a combination of Valsartan and Hydrochlorothiazide (a combination of angiotensin receptor blocker and a thiazide diuretic). It is available as 80/12.5 and 160/12.5 mg for the treatment of hypertension.

Indications of Valsartan and Hydrochlorothiazide (Co Diovan):

• Hypertension:

  • It is indicated for the management of hypertension (as a first-line, add-on, or as a substitute for titrated components)

Valsartan hydrochlorothiazide (Co Diovan) dose in adults:

Co Diovan dose in the treatment of Hypertension:

Note: The doses are individualized. It is prescribed as a first-line or as a substitute for individual components in the patients that are maintained on both the agents separately or when single agents are not effective.

• Initial therapy:

  • Valsartan 160 mg/hydrochlorothiazide 12.5 mg per oral once a day, titrate as required based on the response of patients after 1 to 2 weeks of therapy.

• Maximum daily  dose:

  • Valsartan 320 mg/hydrochlorothiazide 25 mg.

• Add-on/ replacement therapy:

  • Valsartan 80 to 320 mg/hydrochlorothiazide 12.5 to 25 mg per oral once a day; titrate as required based on the patients' response after 3 to 4 weeks of therapy.

• Maximum daily dose:

  • Valsartan 320 mg/hydrochlorothiazide 25 mg.

Valsartan Hydrochlorothiazide (Co Diovan) use in children:

The safety and efficacy of the drug in children have not been established.

Pregnancy Risk Category: D

[US Boxed Warning]

• This is not recommended during pregnancy, as the drug can cause injury or death to the fetus.
• If you become pregnant, it should be stopped immediately
• Also, see the individual agents (Valsartan and Hydrochlorothiazide).

Co Diovan use during breastfeeding:

• Breast milk contains hydrochlorothiazide. It is unknown what happens to valsartan in breast milk.
• Manufacturers do not recommend breastfeeding due to the potential for adverse effects on the fetus.
• Talk to individual agents.

Valsartan and Hydrochlorothiazide (Co Diovan) Dose adjustment in renal disease:

• If Creatinine clearance ≥30 mL/minute:

  • Dosage adjustment is not required.

• If Creatinine clearance <30 mL/minute:

  • It is contraindicated in patients with anuria.
  • The manufacturer has not recommended any dose adjustment in patients with CrCl of less than 30 ml/min.

Valsartan and Hydrochlorothiazide dose in liver disease:

• Mild to moderate impairment:

  • Dose adjustment is not required but caution must be used.
  • Patients with mild to moderate chronic disease have twice the exposure of valsartan as healthy volunteers.

• Severe impairment:

  • There are no dosage adjustments provided in the manufacturer’s labeling.

Common Side Effects of Valsartan and hydrochlorothiazide (Co Diovan):

• Renal:

  • Increased blood urea nitrogen

Less Common Side Effects of Valsartan and hydrochlorothiazide (C0 Diovan):

• Cardiovascular:

  • Hypotension

• Central Nervous System:

  • Dizziness

• Endocrine & Metabolic:

  • Hypokalemia

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Nasopharyngitis

Rare Side effects of Valsartan and Hydrochlorothiazide (Co Diovan):

• Cardiovascular:

  • Chest Pain
  • Orthostatic Hypotension
  • Palpitations
  • Peripheral Edema
  • Tachycardia

• Central Nervous System:

  • Anxiety
  • Drowsiness
  • Fatigue
  • Insomnia
  • Paresthesia
  • Vertigo

• Dermatologic:

  • Hyperhidrosis
  • Skin Rash

• Gastrointestinal:

  • Abdominal Pain
  • Diarrhea
  • Dyspepsia
  • Flatulence
  • Nausea
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Pollakiuria

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Myalgia
  • Weakness

• Otic:

  • Tinnitus

• Respiratory:

  • Cough
  • Dyspnea

• Miscellaneous:

  • Fever

Contraindication to Valsartan and hydrochlorothiazide:

• Hypersensitivity to valsartan, hydrochlorothiazide, sulfonamide-derived drugs, or any component of the formulation
• Anuria
• Combination therapy with aliskiren in patients with diabetes mellitus
• Pregnancy,
• Breastfeeding
• Hyponatremia and hypercalcemia
• Hyperuricemia
• Hypokalemia can result from certain conditions
• Grave progressive renal disease
• Treatment can lead to an increase in azotemia or oliguria.
• Combination therapy with Aliskiren for patients with moderate or severe renal impairment (GFR 60mL/minute/1.73m2).

Notice:

• Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. 
• See "Warnings/Precautions" for more detail.

Warnings and precautions

• Angioedema

  • Angiotensin II receptor inhibitors (ARBs), can cause angioedema during any treatment.
  • It could involve the head, neck (potentially compromising your airway), or the intestine (possibly causing abdominal pain).
  • Patients with idiopathic, hereditary or other forms of angioedema are at greater risk.
  • Regular monitoring is necessary in the event of involvement of the tongue, glottis or larynx. This is especially true if there has been any previous airway surgery.
  • In the event of angioedema, therapy should be stopped immediately. Intramuscular epinephrine should also be administered.
  • Patients with angioedema caused by ARBs should not be used.

• Electrolyte disturbances:

  • Hyperkalemia can be caused by ARBs. Therefore, caution and close monitoring are advised.
  • The risk of developing DM, renal dysfunction, a combination potassium-sparing diuretics or potassium supplements, and potassium-containing salts, increased.
  • Hypokalemia, hypochloremic acidosis, hypomagnesemia and hyponatremia can all be caused by Thiazide diuretics.

• Gout

  • Gout can be caused by hydrochlorothiazide, especially if the dose is greater than 25 mg
  • Patients with chronic renal disease, history of gout, or a family history of gout are at greater risk.

• Hypersensitivity reactions

  • Hypersensitivity reactions to HYdrochlorothiazide may occur in patients who have had a history of asthma or allergy.

• Hypotension

  • Hypotension is common in patients who have had heart surgery or are recovering from a previous MI.
  • Patients with salt- and volume-depletion (eg those who have been treated with high dose diuretics) are at greater risk. Therefore, volume correction before starting treatment is recommended.
  • This transient hypotensive response is not a contraindication to further treatment with valsartan/hydrochlorothiazide.

• Ocular effects

  • Early hydrochlorothiazide therapy can lead to acute transient myopia or angle-closure glaucoma.
  • Patients suffering from severe visual impairments or ocular pain should not be treated.
  • Penicillin allergy or sulfonamide allergy can increase the risk.
  • If intraocular pressure is not controlled, additional treatments may be required.

• Photosensitivity

  • Photosensitization can occur.

• Renal function deterioration:

  • Creatinine levels can be raised in the initial therapy.
  • Therapy can lead to deranged renal function, including oliguria and acute renal failure in patients with low renal blood flow.
  • If there is significant deterioration, it is best to stop the therapy.

• Allergy to sulfonamide ("sulfa")

  • FDA-approved product labels for medications that contain sulfonamide chemical groups include a wide contraindication for patients who have had an allergic reaction to sulfonamides in the past.
  • Cross-reactivity is possible with any two antibiotic sulfonamides.
  • Cross-reactivity concerns have been raised previously for all compounds with the sulfonamide structural (SO NH).
  • Cross-reactivity between non-antibiotic sulfonamides or antibiotic sulfonamides might not occur. This is based on an increased understanding of allergic mechanisms.
  • Non-antibiotic sulfonamides are not likely to cause cross-reactions due to antibody production (anaphylaxis).
  • T-cell-mediated (type IV), reactions (e.g. maculopapular skin rash) are less understood. It is difficult to exclude this possibility based on current knowledge.
  • Treatment is not recommended for severe reactions, such as Stevens Johnson syndrome or toxic epidermal necrolysis.

• Aortic/mitral stenosis:

  • Patients with severe aortic/mitralstenosis should be cautious.

• Bariatric surgery

  • It is important to avoid diuretics during the first 24 hours after bariatric surgery. They can cause electrolyte imbalance and dehydration.
  • Once the oral fluid intake has been sufficient, diuretics can be resumed.

• Diabetes:

  • Patients with diabetes mellitus or prediabetes should exercise caution when giving hydrochlorothiazide, as it can cause a change in glucose control.

• Hepatic impairment

  • Patients with severe hepatic impairment or biliary obstruction should be cautious about using the drug.
  • Hepatic encephalopathy/coma can be caused by electrolyte or acid/base imbalances.

• Hypercalcemia:

  • Thiazides decrease renal calcium excretion so it is not recommended for patients with hypercalcemia.

• Hypercholesterolemia:

  • Patients with high cholesterol should be cautious when taking Thiazide.

• Parathyroid disease

  • You can see decreased calcium excretion and pathologic changes in parathyroid glands associated with hypercalcemia or hypophosphatemia after long-term thiazide treatment.
  • You should not take the drug until you have tested for parathyroid function.

• Renal artery stenosis

  • Valsartan can increase the risk of renal dysfunction. Therefore, it is important to be cautious with unstented unilateral/bilateral renal arterial stenosis.
  • If unstented bilateral renal arterial stenosis exists, it is best to avoid use unless the benefits outweigh the risks.

• Renal impairment

  • Anuria is a contraindication to the drug
    • Valsartan should only be used in severe renal impairment and pre-existing renal disease.
    • Hydrochlorothiazide can precipitate azotemia.
    • If severe renal impairment is observed, the drug should be stopped.

• Systemic lupus erythematosus (SLE):

  • SLE activation or exacerbation can be caused by hydrochlorothiazide.

Monitoring parameters:

• Pulse
• BP
• Serum electrolytes
• Renal function tests

How to administer Co Diovan (Valsartan and hydrochlorothiazide)?

• It should be taken orally with or without food.

Mechanism of action of Valsartan and hydrochlorothiazide (Co Diovan):

• Valsartan, unlike the ACE inhibitors and direct antagonists of the angiotensin II receptors (AT2), acts by displacing the AT1 receptor with angiotensin II. It lowers blood pressure by antagonizing AT1 vasoconstriction and aldosterone, catecholamine, and arginine vasopressin releases, as well as water intake and hypertrophic reactions. It is more effective than ACE inhibitors and has fewer side effects.
• Hydrochlorothiazide increases sodium excretion, water, potassium and hydrogen ions. It inhibits sodium reabsorption from the distal tubules.

See Valsartan and Hydrochlorothiazide

International Brands of Valsartan and hydrochlorothiazide:

• Aralter Plus
• Cardisar
• Cardival Plus
• Co-Aginet
• Co-Bespres
• Co-Dio
• Co-Diopass
• Co-Diovan
• Co-Diovane
• Co-Dopcor
• Co-Tareg
• Codiortan
• CoDiovan
• Codiqvan
• Corixil
• Cotareg
• Covaratan
• Detension
• Diovan Comp
• Diovan D
• Diovan HCT
• Dizantin Plus
• Duotan
• Duoval
• Duovan
• Dynaval
• Hapresval Plus
• Kalpress Plus
• Maxdioplus
• Miten Plus
• Nisisco
• Sakord H
• Simultan D
• Tareg D
• Tensart HCT
• V-Van Plus
• Valazyd-H
• Valent-H
• Valsaprex-H
• Valsartan/HCT
• Valsotens HCT
• Valtan H
• Valtan Plus
• Valtensin HCT
• Valzaar-H
• Vector Plus

Valsartan and hydrochlorothiazide Brand Names in Pakistan:

Valsartan and Hydrochlorothiazide 80/12.5 mg

Valsasartan And Hydrochlorothiazide 160/12.5 Mg