Side Effects of Kapvay (clonidine extended-release)

Kapvay (clonidine extended-release) is a centrally acting alpha2-adrenergic agonist used to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents. 

Kapvay has been used to reduce blood pressure in adults for many years but has been approved for another indication by the FDA. Kapvay works by stimulating alpha-2 receptors in the brain. This may reduce hyperactivity symptoms by acting on parts of the brain that control emotion, attention and behavior. The exact mechanism in treating ADHD is not known.

Common side effects of Kapvay include

• drowsiness,
• fatigue,
• cough,
• runny nose,
• sore throat,
• dry mouth,
• hallucinations,
• constipation, and
• insomnia. 

Serious side effects of Kapvay include

• reductions in blood pressure and heart rate, which can be severe.

Drug interactions of Kapvay include alcohol or other sedating drugs such as lorazepam due to increased risk of drowsiness. 

Combining Kapvay with medications that can affect heart rate such as diltiazem and atenolol can lead to a severe decrease in heart rate. 

Tricyclic antidepressants such as amitriptyline can reduce the antihypertensive effects of Kapvay by blocking its receptors. 

Kapvay should not be combined with other clonidine containing medications such as Catapres. 

Kapvay should be used carefully in patients taking other medications that reduce blood pressure due to risk of excessive blood pressure reduction. 

There are no adequate or well-controlled studies with Kapvay in pregnant women. 

Kapvay is secreted into breast milk and should be used cautiously in women who are breastfeeding.

The most common side effects associated with Kapvay are

• drowsiness,
• fatigue,
• cough,
• runny nose, and
• sore throat.

Kapvay can also cause

• dry mouth,
• hallucinations,
• constipation and
• insomnia.

Reductions in blood pressure and heart rate, which can be severe, have also been reported.

The following serious adverse reactions are described in greater detail elsewhere in labeling:

• Hypotension/bradycardia
• Sedation and somnolence
• Rebound hypertension
• Allergic reactions
• Cardiac Conduction Abnormalities

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Two Kapvay ADHD clinical studies (Study 1, CLON-301 and Study 2, CLON-302) evaluated 256 patients in two 8-week placebo-controlled studies.

A third Kapvay ADHD clinical study (Study 3, SHN-KAP-401) evaluated 135 children and adolescents in a 40- week placebo-controlled randomized-withdrawal study.

Study 1: Fixed-dose Kapvay Monotherapy

Study 1 (CLON-301) was a short-term, multi-center, randomized, double-blind, placebo-controlled study of two fixed doses (0.2 mg/day or 0.4 mg/day) of Kapvay in children and adolescents (6 to 17 years of age) who met DSM-IV criteria for ADHD hyperactive or combined inattentive/hyperactive subtypes.

Most Common Adverse Reactions (incidence of ≥ 5% and at least twice the rate of placebo):

• somnolence,
• fatigue,
• irritability,
• insomnia,
• nightmare,
• constipation,
• dry mouth.

Adverse Events Leading to Discontinuation of Kapvay – Five patients (7%) in the low dose group (0.2 mg), 15 patients (20%) in the high dose group (0.4 mg), and 1 patient in the placebo group (1%) reported adverse reactions that led to discontinuation.

The most common adverse reactions that led to discontinuation were somnolence and fatigue.

Commonly observed adverse reactions (incidence of ≥ 2% in either active treatment group and greater than the rate on placebo) during the treatment period are listed in Table 2.

Table 2 : Common Adverse Reactions in the Fixed-Dose Monotherapy Trial- Treatment Period (Study 1)

Commonly observed adverse reactions (incidence of ≥ 2% in either active treatment group and greater than the rate on placebo) during the taper period are listed in Table 3.

Table 3 : Common Adverse Reactions in the Fixed-Dose Monotherapy Trial- Taper Period* (Study 1)

Study 2: Flexible-dose Kapvay as Adjunctive Therapy to Psychostimulants

Study 2 (CLON-302) was a short-term, randomized, double-blind, placebo-controlled study of a flexible dose of Kapvay as adjunctive therapy to a psychostimulant in children and adolescents (6 to 17 years) who met DSM-IV criteria for ADHD hyperactive or combined inattentive/hyperactive subtypes, during which Kapvay was initiated at 0.1 mg/day and titrated up to 0.4 mg/day over a 3-week period.

Most Kapvay treated patients (75.5%) were escalated to the maximum dose of 0.4 mg/day.

Most Common Adverse Reactions (incidence of ≥ 5% and at least twice the rate of placebo):

• somnolence,
• fatigue,
• decreased appetite,
• dizziness.

Adverse Events Leading to Discontinuation –There was one patient in the CLON+STM group (1%) who discontinued because of an adverse event (severe bradyphrenia, with severe fatigue).

Commonly observed adverse reactions (incidence of ≥ 2% in the treatment group and greater than the rate on placebo) during the treatment period are listed in Table 4.

Table 4 : Common Adverse Reactions in the Flexible-Dose Adjunctive to Stimulant Therapy Trial- Treatment Period (Study 2)

Commonly observed adverse reactions (incidence of ≥ 2% in the treatment group and greater than the rate on placebo) during the taper period are listed in Table 5.

Table 5 : Common Adverse Reactions in the Flexible-Dose Adjunctive to Stimulant Therapy Trial- Taper Period* (Study 2)

Adverse Reactions Leading to Discontinuation

Thirteen percent (13%) of patients receiving Kapvay discontinued from the pediatric monotherapy study due to adverse events, compared to 1% in the placebo group. The most common adverse reactions leading to discontinuation of Kapvay monotherapy treated patients were from somnolence/sedation (5%) and fatigue (4%).

Effect on Blood Pressure and Heart Rate

• In patients that completed 5 weeks of treatment in a controlled, fixed-dose monotherapy study in pediatric patients, during the treatment period the maximum placebo-subtracted mean change in systolic blood pressure was -4.0 mmHg on Kapvay 0.2 mg/day and -8.8 mmHg on Kapvay 0.4 mg/day.
• The maximum placebo-subtracted mean change in diastolic blood pressure was -4.0 mmHg on Kapvay 0.2 mg/day and -7.3 mmHg on Kapvay 0.4 mg/day. The maximum placebo-subtracted mean change in heart rate was -4.0 beats per minute on Kapvay 0.2 mg/day and -7.7 beats per minute on Kapvay 0.4 mg/day.
• During the taper period of the fixed-dose monotherapy study the maximum placebo-subtracted mean change in systolic blood pressure was +3.4 mmHg on Kapvay 0.2 mg/day and -5.6 mmHg on Kapvay 0.4 mg/day.
• The maximum placebo-subtracted mean change in diastolic blood pressure was +3.3 mmHg on Kapvay 0.2 mg/day and -5.4 mmHg on Kapvay 0.4 mg/day.
• The maximum placebo-subtracted mean change in heart rate was -0.6 beats per minute on Kapvay 0.2 mg/day and -3.0 beats per minute on Kapvay 0.4 mg/day.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Kapvay. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events exclude those already mentioned in 6.1:

Psychiatric: hallucinations

Cardiovascular: Q-T prolongation

The following have been reported with other oral immediate release formulations of clonidine:

Table 6 : Clinically Important Drug Interactions

Drug Abuse And Dependence

Controlled Substance

Kapvay is not a controlled substance and has no known potential for abuse or dependence.