July 29, 2015
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Kapvay

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Kapvay

Side Effects
Interactions

SIDE EFFECTS

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

  • Hypotension/bradycardia [see WARNINGS AND PRECAUTIONS]
  • Sedation and somnolence [see WARNINGS AND PRECAUTIONS]
  • Rebound hypertension [see WARNINGS AND PRECAUTIONS]
  • Allergic reactions [see WARNINGS AND PRECAUTIONS]
  • Cardiac Conduction Abnormalities [see WARNINGS AND PRECAUTIONS]

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)

Preferred Term Percentage of Patients Reporting Event
KAPVAY 0.2 mg/day
N=76
KAPVAY 0.4 mg/day
N=78
Placebo
(N=76)
PSYCHIATRIC DISORDERS
  Somnolence* 38% 31% 4%
  Nightmare 4% 9% 0%
  Emotional Disorder 4% 4% 1%
  Aggression 3% 1% 0%
  Tearfulness 1% 3% 0%
  Enuresis 0% 4% 0%
  Sleep Terror 3% 0% 0%
  Poor Quality Sleep 0% 3% 1%
NERVOUS SYSTEM DISORDERS
  Headache 20% 13% 16%
  Insomnia 5% 6% 1%
  Tremor 1% 4% 0%
  Abnormal Sleep-Related Event 3% 1% 0%
GASTROINTESTINAL DISORDERS
  Upper Abdominal Pain 15% 10% 12%
  Nausea 4% 5% 3%
  Constipation 1% 6% 0%
  Dry Mouth 0% 5% 1%
GENERAL DISORDERS
  Fatigue† 16% 13% 1%
  Irritability 9% 5% 4%
CARDIAC DISORDERS
  Dizziness 7% 3% 5%
  Bradycardia 0% 4% 0%
INVESTIGATIONS
  Increased Heart Rate 0% 3% 0%
METABOLISM AND NUTRITION DISORDERS
  Decreased Appetite 3% 4% 4%
* Somnolence includes the terms “somnolence” and “sedation”.
† Fatigue includes the terms “fatigue” and “lethargy”.

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)

Preferred Term Percentage of Patients Reporting Event
KAPVAY 0.2 mg/day
N=76
KAPVAY 0.4 mg/day
N=78
Placebo
(N=76)
Abdominal Pain Upper 0% 6% 3%
Headache 5% 2% 3%
Gastrointestinal Viral 0% 5% 0%
Somnolence 2% 3% 0%
Heart Rate Increased 0% 3% 0%
Otitis Media Acute 1 3% 1 0% 1 0%
* Taper Period: 0.2 mg dose, week 8; 0.4 mg dose, weeks 6-8; Placebo dose, weeks 6-8

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)

Preferred Term Percentage of Patients Reporting Event
KAPVAY+STM
(N=102)
PBO+STM
(N=96)
PSYCHIATRIC DISORDERS
  Somnolence* 19% 7%
  Aggression 2% 1%
  Affect Lability 2% 1%
  Emotional Disorder 2% 0%
GENERAL DISORDERS
  Fatigue† 14% 4%
  Irritability 2% 7%
NERVOUS SYSTEM DISORDERS
  Headache 7% 12%
  Insomnia 4% 3%
GASTROINTESTINAL DISORDERS
  Upper Abdominal Pain 7% 4%
RESPIRATORY DISORDERS
  Nasal Congestion 2% 2%
METABOLISM AND NUTRITION DISORDERS
  Decreased Appetite 6% 3%
CARDIAC DISORDERS
  Dizziness 5% 1%
* Somnolence includes the terms: “somnolence” and “sedation”.
† Fatigue includes the terms “fatigue” and “lethargy”.

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)

Preferred Term Percentage of Patients Reporting Event
KAPVAY+STM
(N=102)
PBO+STM
(N=96)
Nasal Congestion 4% 2%
Headache 3% 1%
Irritability 3% 2%
Throat Pain 3% 1%
Gastroenteritis Viral 2% 0%
Rash 2% 0%
* Taper Period: weeks 6-8

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

Read the Kapvay (clonidine hydrochloride extended-release tablets) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

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

Table 6 : Clinically Important Drug Interactions

Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation
Tricyclic antidepressants Increase blood pressure and may counteract clonidine’s hypotensive effects Monitor blood pressure and adjust as needed
Antihypertensive drugs Potentiate clonidine’s hypotensive effects Monitor blood pressure and adjust as needed
CNS depressants Potentiate sedating effects Avoid use
Drugs that affect sinus node function or AV node conduction (e.g., digitalis, calcium channel blockers, beta blockers) Potentiate bradycardia and risk of AV block Avoid use

Drug Abuse And Dependence

Controlled Substance

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

Last reviewed on RxList: 7/1/2015
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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