Triamterene/Hydrochlorothiazide

Uses and Indications

Triamterene and hydrochlorothiazide is indicated for the treatment of hypertension or edema in patients who develop hypokalemia on hydrochlorothiazide alone. This fixed combination drug is also indicated for patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked, such as those on concomitant digitalis preparations or with a history of cardiac arrhythmias. Triamterene and hydrochlorothiazide may be used alone or as an adjunct to other antihypertensive drugs, including beta-blockers. Since this combination may enhance the action of these agents, dosage adjustments may be necessary.

Limitations of Use

This fixed combination drug is not indicated for the initial therapy of edema or hypertension except in individuals in whom the development of hypokalemia cannot be risked.

Teratogenic Effects

The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes both mother and fetus to unnecessary hazards. Diuretics do not prevent the development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

Nonteratogenic Effects

Edema during pregnancy may arise from pathological causes or from the physiological and mechanical consequences of pregnancy. Diuretics are indicated in pregnancy when edema is due to pathological causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose; the use of diuretics to lower intravascular volume in this case is illogical and unnecessary.

There is hypervolemia during normal pregnancy, which is not harmful to either the fetus or the mother (in the absence of cardiovascular disease), but is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort that is not relieved by rest. In these cases, a short course of diuretics may provide relief and may be appropriate.

Dosage and Administration

The usual dosage of triamterene and hydrochlorothiazide is as follows:

For the capsule formulation, the recommended dose is one or two capsules taken once daily. Appropriate monitoring of serum potassium and clinical effects is advised.

For the tablet formulation, the usual doses are:

• 37.5 mg/25 mg tablets: One or two tablets daily, administered as a single dose, with appropriate monitoring of serum potassium.

• 75 mg/50 mg tablets: One tablet daily, with appropriate monitoring of serum potassium.

There is no clinical experience with the use of more than one 75 mg/50 mg tablet daily or more than two 37.5 mg/25 mg tablets daily. Clinical experience indicates that administering two 37.5 mg/25 mg tablets daily in divided doses may increase the risk of electrolyte imbalance and renal dysfunction.

In patients requiring hydrochlorothiazide therapy who cannot risk hypokalemia, therapy may be initiated with the 37.5 mg/25 mg formulation. If an optimal blood pressure response is not achieved with this dosage, the dose may be increased to two 37.5 mg/25 mg tablets daily as a single dose or one 75 mg/50 mg tablet daily. If blood pressure remains uncontrolled, consideration should be given to adding another antihypertensive agent.

Patients receiving 50 mg of hydrochlorothiazide who become hypokalemic may be transitioned directly to the 75 mg/50 mg formulation. Similarly, patients receiving 25 mg of hydrochlorothiazide who become hypokalemic may be transitioned directly to the 37.5 mg/25 mg formulation.

Clinical studies have demonstrated that patients taking less bioavailable formulations of triamterene and hydrochlorothiazide in daily doses of 25 mg to 50 mg hydrochlorothiazide and 50 mg to 100 mg triamterene may be safely switched to one 37.5 mg/25 mg tablet daily. All patients transitioning from less bioavailable formulations to the 75 mg/50 mg formulation should be monitored clinically and for serum potassium following the transfer.

Contraindications

Triamterene and hydrochlorothiazide are contraindicated in patients with elevated serum potassium levels (greater than or equal to 5.5 mEq/liter). If hyperkalemia develops, discontinuation of this medication and substitution with a thiazide alone is recommended.

The use of triamterene and hydrochlorothiazide is also contraindicated in patients receiving other potassium-sparing agents, such as spironolactone or amiloride, as well as in those using potassium supplementation in any form, including potassium-containing salt substitutes or potassium-enriched diets.

Patients with anuria, acute or chronic renal insufficiency, or significant renal impairment should not be treated with triamterene and hydrochlorothiazide due to the risk of further renal compromise.

Additionally, hypersensitivity to either triamterene or hydrochlorothiazide, or to other sulfonamide-derived drugs, constitutes a contraindication for the use of this medication.

Warnings and Precautions

Abnormal elevation of serum potassium levels (greater than or equal to 5.5 mEq/liter) can occur with all potassium-sparing diuretic combinations, including triamterene and hydrochlorothiazide. Hyperkalemia is more likely to occur in patients with renal impairment, diabetes (even without evidence of renal impairment), and in the elderly or severely ill. Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals, especially in patients first receiving triamterene and hydrochlorothiazide, when dosages are changed, or with any illness that may influence renal function.

Serious Warnings

If hyperkalemia is suspected, warning signs include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, and shock. An electrocardiogram (ECG) should be obtained. If hyperkalemia is present, triamterene and hydrochlorothiazide should be discontinued immediately, and a thiazide alone should be substituted. If the serum potassium exceeds 6.5 mEq/liter, more vigorous therapy is required, which may include intravenous administration of calcium chloride solution, sodium bicarbonate solution, and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation. Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis.

The development of hyperkalemia associated with potassium-sparing diuretics is accentuated in the presence of renal impairment. Patients with mild renal functional impairment should not receive this drug without frequent and continuing monitoring of serum electrolytes. Cumulative drug effects may be observed in patients with impaired renal function. Hyperkalemia has been reported in diabetic patients with the use of potassium-conserving agents even in the absence of apparent renal impairment. Accordingly, serum electrolytes must be frequently monitored if triamterene and hydrochlorothiazide is used in diabetic patients.

General Precautions

Patients receiving triamterene and hydrochlorothiazide should be carefully monitored for fluid or electrolyte imbalances, including hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia. Determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. Serum and urine electrolyte determinations are especially important and should be frequently performed when the patient is vomiting or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Triamterene and hydrochlorothiazide may produce an elevated blood urea nitrogen (BUN) level, creatinine level, or both. Periodic BUN and creatinine determinations should be made, especially in elderly patients, patients with suspected or confirmed hepatic disease, or renal insufficiencies. If azotemia increases, triamterene and hydrochlorothiazide should be discontinued. The use of this medication should be approached with caution in patients with impaired hepatic function or progressive liver disease, as minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Laboratory Tests

Serum potassium levels must be monitored at frequent intervals, especially in patients first receiving triamterene and hydrochlorothiazide, when dosages are changed, or with any illness that may influence renal function. Periodic BUN and creatinine determinations should be made, especially in elderly patients, patients with suspected or confirmed hepatic disease, or renal insufficiencies. Thiazides should be discontinued before carrying out tests for parathyroid function, as calcium excretion is decreased by thiazides.

Get Emergency Medical Help

If hyperkalemia is suspected, an electrocardiogram (ECG) should be obtained. If hyperkalemia is present, triamterene and hydrochlorothiazide should be discontinued immediately.

Stop Taking and Call Your Doctor

If hyperkalemia is present, triamterene and hydrochlorothiazide should be discontinued immediately and a thiazide alone should be substituted. If azotemia increases, triamterene and hydrochlorothiazide should be discontinued.

Side Effects

Patients receiving triamterene and hydrochlorothiazide may experience a range of adverse reactions, which can be categorized by seriousness and frequency. The following outlines the reported adverse reactions based on clinical trial and postmarketing data.

Serious Adverse Reactions

• Hyperkalemia: Abnormal elevation of serum potassium levels (≥5.5 mEq/liter) can occur, particularly in patients with renal impairment, diabetes, or those who are elderly or severely ill. Uncorrected hyperkalemia may be fatal, necessitating frequent monitoring of serum potassium levels, especially when initiating therapy or adjusting dosages.

• Acute Renal Failure: Cases of acute renal failure, including one report of irreversible renal failure, have been documented.

• Severe Hypersensitivity Reactions:

  • Anaphylaxis

  • Erythema multiforme, including Stevens-Johnson syndrome

  • Exfoliative dermatitis, including toxic epidermal necrolysis

• Hematologic Disorders:

  • Agranulocytosis

  • Aplastic anemia

  • Hemolytic anemia

Common Adverse Reactions

Cardiovascular

• Arrhythmia

• Postural hypotension

• Tachycardia

• Shortness of breath and chest pain

Gastrointestinal

• Jaundice (intrahepatic cholestatic jaundice)

• Pancreatitis

• Nausea and vomiting

• Diarrhea

• Constipation

• Abdominal pain

• Appetite disturbance

• Taste alteration

• Gastric irritation

• Cramping

Central Nervous System

• Weakness

• Fatigue

• Dizziness

• Headache

• Dry mouth

• Paresthesias

• Vertigo

• Drowsiness

• Insomnia

• Depression

• Anxiety

• Restlessness

Renal

• Interstitial nephritis

• Renal stones composed primarily of triamterene

• Elevated BUN and serum creatinine

• Urine discoloration

Hematologic

• Leukopenia

• Thrombocytopenia and purpura

• Megaloblastic anemia

Ophthalmic

• Xanthopsia

• Transient blurred vision

Respiratory

• Allergic pneumonitis

• Pulmonary edema

• Respiratory distress

Miscellaneous

• Muscle cramps

• Impotence

• Sialadenitis

• Necrotizing vasculitis

• Exacerbation of lupus

Neonate and Infancy

• Thrombocytopenia and pancreatitis have been reported rarely in newborns whose mothers received thiazides during pregnancy.

Postmarketing Experience

• Non-Melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer, predominantly squamous cell carcinoma (SCC) in white patients taking large cumulative doses. The risk for SCC in the overall population is approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg, the risk increase is approximately 1 additional SCC case for every 6,700 patients per year.

Warnings

• Patients should be monitored for fluid or electrolyte imbalances, including hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia. Warning signs include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle cramps, hypotension, and gastrointestinal disturbances.

• Acute Myopia and Secondary Angle-Closure Glaucoma: Hydrochlorothiazide can cause an idiosyncratic reaction resulting in acute transient myopia and acute angle-closure glaucoma, which may lead to permanent vision loss if untreated.

• Hepatic Coma: Use with caution in patients with impaired hepatic function or progressive liver disease, as minor alterations in fluid and electrolyte balance may precipitate hepatic coma.

• Folic Acid Deficiency: Triamterene is a weak folic acid antagonist and may contribute to megaloblastosis in patients with decreased folic acid stores.

• Hyperuricemia: May occur or acute gout may be precipitated in certain patients receiving thiazide therapy.

Drug Interactions

Concurrent use of triamterene and hydrochlorothiazide with other medications requires careful consideration due to potential drug interactions, which can be categorized into pharmacokinetic and pharmacodynamic interactions.

Pharmacokinetic Interactions

• Angiotensin-Converting Enzyme (ACE) Inhibitors: Potassium-sparing agents like triamterene should be used with caution alongside ACE inhibitors due to an increased risk of hyperkalemia. Frequent monitoring of serum potassium levels is recommended.

• Lithium: The use of diuretics, including triamterene and hydrochlorothiazide, can reduce the renal clearance of lithium, significantly increasing the risk of lithium toxicity. Caution is advised, and the prescribing information for lithium should be consulted before concurrent therapy.

• Oral Anticoagulants: The effectiveness of oral anticoagulants may be diminished when used with hydrochlorothiazide, necessitating dosage adjustments.

• Indomethacin and Other Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): There have been reports of acute renal failure in patients receiving indomethacin in conjunction with triamterene and hydrochlorothiazide. Caution is advised when administering NSAIDs with these medications.

• Methenamine: The effectiveness of methenamine may be reduced when used concurrently with hydrochlorothiazide due to the alkalinization of urine.

Pharmacodynamic Interactions

• Electrolyte Imbalance: Concurrent use of hydrochlorothiazide with amphotericin B, corticosteroids, or corticotropin (ACTH) may exacerbate electrolyte imbalances, particularly hypokalemia. However, the presence of triamterene may mitigate this effect.

• Chlorpropamide: The combination of triamterene and chlorpropamide may increase the risk of severe hyponatremia.

• Norepinephrine and Muscle Relaxants: Thiazides, including hydrochlorothiazide, may decrease arterial responsiveness to norepinephrine, although this does not preclude the effectiveness of pressor agents. Additionally, thiazides can enhance the effects of nondepolarizing muscle relaxants, such as tubocurarine, due to potassium loss, warranting caution in surgical settings.

• Uric Acid Levels: Triamterene and hydrochlorothiazide may elevate blood uric acid levels, which could necessitate dosage adjustments of antigout medications to manage hyperuricemia and gout.

Laboratory Test Interactions

• Quinidine Measurement: Triamterene and hydrochlorothiazide may interfere with the fluorescent measurement of quinidine due to their similar fluorescence spectra.

Other Considerations

• Potassium-Rich Substances: Certain substances, such as blood products, low-salt milk, potassium-containing medications, and salt substitutes, may contribute to serum potassium accumulation when used with triamterene, particularly in patients with renal insufficiency.

• Laxatives: Chronic or excessive use of laxatives may lead to reduced serum potassium levels, counteracting the potassium-retaining effects of triamterene.

In summary, careful monitoring and consideration of potential interactions are essential when prescribing triamterene and hydrochlorothiazide in conjunction with other medications.

Pediatric Use

Safety and effectiveness of Triamterene and Hydrochlorothiazide in pediatric patients have not been established. This applies to both capsule and tablet formulations. No specific age ranges, dosing details, or study outcomes are available for pediatric use. Caution is advised when considering this medication for children and adolescents.

Geriatric Use

Hyperkalemia is more likely to occur in elderly patients, particularly those with renal impairment or diabetes. Serum potassium levels must be monitored at frequent intervals, especially when elderly patients are first receiving triamterene and hydrochlorothiazide, when dosages are changed, or during any illness that may influence renal function.

The renal clearances of hydrochlorothiazide and the pharmacologically active metabolite of triamterene are reduced in elderly patients, leading to increased plasma levels of these medications. Cumulative drug effects may also be observed in elderly patients with impaired renal function.

Periodic determinations of blood urea nitrogen (BUN) and serum creatinine should be conducted, particularly in elderly patients and those with suspected or confirmed renal insufficiency. Patients with mild renal functional impairment should not receive this medication without frequent and ongoing monitoring of serum electrolytes.

Pregnancy

The safe use of triamterene and hydrochlorothiazide in pregnancy has not been established due to the absence of adequate and well-controlled studies in pregnant women. Both triamterene and hydrochlorothiazide are classified as Pregnancy Category C, indicating that they should be used during pregnancy only if the potential benefits justify the risks to the fetus.

Animal reproduction studies have not been conducted to determine the potential for fetal harm from triamterene and hydrochlorothiazide. However, a One Generation Study in rats, which approximated the drug composition using a 1:1 ratio of triamterene to hydrochlorothiazide (30:30 mg/kg/day), showed no evidence of teratogenicity at doses significantly higher than the maximum recommended human dose (MRHD). Specifically, these doses were 15 and 30 times the MRHD on a body-weight basis, and 3.1 and 6.2 times the MRHD on a body-surface area basis.

Reproduction studies in rats have demonstrated that doses up to 20 times the MRHD (body-weight) and 6 times the MRHD (body-surface area) of triamterene did not result in fetal harm. Hydrochlorothiazide, administered to pregnant mice and rats during major organogenesis at doses up to 3,000 mg/kg/day (mice) and 1,000 mg/kg/day (rats), also showed no evidence of harm to the fetus.

Despite these findings, it is important to note that animal studies are not always predictive of human response. Therefore, triamterene and hydrochlorothiazide should be used during pregnancy only if clearly needed. Both drugs have been shown to cross the placental barrier and appear in cord blood. The anticipated benefits of treatment must be weighed against potential hazards to the fetus, which may include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and other adverse reactions that have been observed in adults.

Lactation

Triamterene and hydrochlorothiazide have not been studied in nursing mothers, and therefore, the safety of this combination in lactation is not established. Triamterene has been shown to appear in animal milk, suggesting that it may also be excreted in human breast milk. Additionally, thiazides are known to be excreted in human breast milk.

Given the potential for excretion into breast milk and the lack of data on the effects in breastfed infants, if the use of this combination drug is deemed essential, it is recommended that lactating mothers discontinue breastfeeding. Healthcare providers should weigh the benefits of treatment against the potential risks to the infant when considering this medication for nursing mothers.

Renal Impairment

Patients with renal impairment are at an increased risk of developing hyperkalemia when treated with triamterene and hydrochlorothiazide. This risk is further heightened in individuals with diabetes (even in the absence of renal impairment), as well as in elderly or severely ill patients.

Serum potassium levels must be monitored at frequent intervals, particularly when initiating treatment with triamterene and hydrochlorothiazide, during dosage adjustments, or in the presence of any condition that may affect renal function. If hyperkalemia is suspected or confirmed, the medication should be discontinued immediately, and a thiazide diuretic alone may be substituted. In cases where serum potassium exceeds 6.5 mEq/liter, more aggressive interventions may be necessary, including the administration of calcium chloride, sodium bicarbonate, or insulin with glucose, and persistent hyperkalemia may require dialysis.

Patients with mild renal functional impairment should not receive this combination without ongoing and careful monitoring of serum electrolytes. Cumulative drug effects may occur in those with impaired renal function, as the renal clearances of hydrochlorothiazide and the active metabolite of triamterene are reduced, leading to increased plasma levels.

In diabetic patients, the use of triamterene and hydrochlorothiazide should be approached with caution, and serum electrolytes must be monitored closely. Additionally, potassium-sparing therapy should be avoided in severely ill patients, particularly those at risk for respiratory or metabolic acidosis, as this condition can lead to rapid increases in serum potassium levels. Regular evaluations of acid/base balance and serum electrolytes are essential for patients with acidosis who are treated with this combination.

Hepatic Impairment

Patients with hepatic impairment should use triamterene and hydrochlorothiazide with caution, particularly those with severe liver disease, as thiazides may precipitate hepatic coma. It is essential to monitor for early signs of impending coma, such as confusion, drowsiness, and tremor. If mental confusion increases, discontinuation of triamterene and hydrochlorothiazide may be necessary for a few days.

Additionally, attention must be given to other factors that could precipitate hepatic coma, including gastrointestinal bleeding or pre-existing potassium depletion. No specific dosage adjustments, special monitoring, or additional precautions for patients with liver problems are provided in the available data.

Overdosage

In cases of overdosage with triamterene and hydrochlorothiazide, electrolyte imbalance is the primary concern. Symptoms may include polyuria, nausea, vomiting, weakness, lassitude, fever, flushed face, and hyperactive deep tendon reflexes. Excessive doses of triamterene can lead to hyperkalemia, dehydration, and potentially hypotension, while overdosing with hydrochlorothiazide may result in hypokalemia, hypochloremia, hyponatremia, dehydration, lethargy (which may progress to coma), and gastrointestinal irritation.

Immediate intervention is critical. Induction of emesis or gastric lavage should be performed to evacuate the stomach. There is no specific antidote available for this combination. If hypotension occurs, treatment may involve the use of pressor agents such as levarterenol to maintain blood pressure. Continuous monitoring of serum electrolyte levels and fluid balance is essential, along with supportive measures to ensure hydration and maintain respiratory, cardiovascular, and renal function.

In cases where significant renal impairment is suspected, particularly following the ingestion of large quantities (e.g., 50 tablets containing 50 mg of triamterene and 25 mg of hydrochlorothiazide), dialysis may provide some benefit, despite triamterene being largely protein-bound (approximately 67%). Therapy with triamterene and hydrochlorothiazide should be discontinued immediately upon recognition of an overdose.

Nonclinical Toxicology

Teratogenic Effects

Animal reproduction studies to determine the potential for fetal harm by triamterene and hydrochlorothiazide have not been conducted. However, a One Generation Study in rats, using a 1:1 ratio of triamterene to hydrochlorothiazide (30:30 mg/kg/day), showed no evidence of teratogenicity at doses that were, on a body-weight basis, 15 and 30 times the Maximum Recommended Human Dose (MRHD), and on the basis of body surface area, 3.1 and 6.2 times the MRHD. The safe use of triamterene and hydrochlorothiazide in pregnancy has not been established due to the lack of adequate and well-controlled studies in pregnant women. Therefore, these medications should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Non-Teratogenic Effects

Hydrochlorothiazide has been shown to cross the placental barrier and appear in cord blood. Studies indicate that hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex when these species were exposed, via their diet, to doses of up to 100 mg/kg/day for mice and 4 mg/kg/day for rats prior to mating and throughout gestation. The corresponding multiples of the MRHD are 100 (mice) and 4 (rats) based on body weight, and 9.4 (mice) and 0.8 (rats) based on body surface area. The use of thiazides and triamterene in pregnant women requires careful consideration of the anticipated benefits against possible hazards to the fetus, which may include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and other adverse reactions observed in adults.

Nonclinical Toxicology

Long-term studies with triamterene and hydrochlorothiazide have not been conducted. In studies conducted under the auspices of the National Toxicology Program (NTP), groups of rats and mice were fed diets containing varying concentrations of triamterene. Male and female rats exposed to the highest tested concentration received approximately 25 and 30 mg/kg/day, respectively, while male and female mice received about 45 and 60 mg/kg/day, respectively. An increased incidence of hepatocellular neoplasia (primarily adenomas) was observed in male and female mice at the highest dosage level, which represented 7.5 times and 10 times the MRHD of 300 mg/kg (or 6 mg/kg/day based on a 50 kg patient) for male and female mice, respectively, when based on body weight, and 0.7 times and 0.9 times the MRHD when based on body surface area. Although hepatocellular neoplasia in the rat study was limited to triamterene-exposed males, the incidence was not dose-dependent, and no statistically significant difference from control incidence was noted at any dose level.

Two-year feeding studies in mice and rats treated with hydrochlorothiazide at doses up to 600 mg/kg/day for mice and 100 mg/kg/day for rats revealed no evidence of carcinogenic potential in rats or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in various in vitro assays, including the Ames test and chromosomal aberration tests. Positive results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in mouse lymphoma cell (mutagenicity) assays at specific concentrations. Additionally, studies of the mutagenic potential of triamterene and hydrochlorothiazide have not been performed.

Animal Pharmacology and Toxicology

Studies of the effects of triamterene and hydrochlorothiazide on animal reproductive function have not been conducted. Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies where these species were exposed to doses of up to 100 mg/kg/day and 4 mg/kg/day, respectively, prior to mating and throughout gestation.

Storage and Handling

Triamterene and Hydrochlorothiazide is available in both capsule and tablet forms.

Capsules are supplied in a tight, light-resistant container as defined in the USP, with a child-resistant closure. Tablets are also dispensed in a tight, light-resistant container, with some configurations including a child-resistant closure.

All formulations should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) for certain tablet configurations. It is essential to protect the product from light and moisture.

Additionally, all products should be kept out of reach of children.