sp; Disorders
Hypersensitivity
Investigations
Increased alanine amino transferase, increased weight
Nervous system
Convulsion
Psychiatric
Agitation, anxiety, depression, nightmare
Renal
Increased urinary frequency, enuresis
Respiratory
Asthma
Vascular
Hypertension, pallor
6.2 Post-marketing Experience
The following adverse reactions have been identified during post-approval use of guanfacine. 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.
An open-label post-marketing study involving 21,718 patients was conducted to assess the safety of guanfacine (as the hydrochloride) 1 mg/day given at bedtime for 28 days. Guanfacine was administered with or without other antihypertensive agents. Adverse events reported in the post-marketing study at an incidence greater than 1% included dry mouth, dizziness, somnolence, fatigue, headache and nausea. The most commonly reported adverse events in this study were the same as those observed in controlled clinical trials.
Less frequent, possibly guanfacine-related events observed in the post-marketing study and/or reported spontaneously, not included in , include: SECTION 6.1
edema, malaise, tremor General:
palpitations, tachycardia Cardiovascular:
paresthesias, vertigo Central Nervous System:
blurred vision Eye Disorders:
arthralgia, leg cramps, leg pain, myalgia Musculo-Skeletal System:
confusion, hallucinations Psychiatric:
impotence Reproductive System, Male:
dyspnea Respiratory System:
alopecia, dermatitis, exfoliative dermatitis, pruritus, rash Skin and Appendages:
alterations in taste Special Senses:
7 DRUG INTERACTIONS
Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be affected significantly by CYP3A4 inhibitors or inducers (Figure 1). Dose adjustments are recommended . Guanfacine does not significantly affect exposures of methylphenidate and lisdexamfetamine when coadministered (Figure 2). Therefore, no dose adjustments in methylphenidate or lisdexamfetamine are necessary. [] SEE DOSAGE AND ADMINISTRATION (2.7)
Figure 1: Impact of Other Drugs on the Pharmacokinetics (PK) of Intuniv
Figure 1
Figure 2: Impact of Intuniv on the Pharmacokinetics (PK) of Other Drugs
Figure 2
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B
Risk Summary
There are no adequate and well-controlled studies of INTUNIV in pregnant women. No fetal harm was observed in rats and rabbits with administration of guanfacine at 6 and 4 times, respectively, the maximum recommended human dose. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Animal data
Reproduction studies conducted in rats have shown that guanfacine crosses the placenta. However, administration of guanfacine to rats and rabbits at 6 and 4 times, respectively, the maximum recommended human dose of 4 mg/day
